Implantable pressure sensors

ABSTRACT

Implantable pressure sensors and methods for making and using the same are provided. A feature of embodiments of the subject pressure sensors is that they are low-drift sensors. The subject sensors find use in a variety of applications.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a continuation which claims priority toPCT/US ______ (Atty. Docket No. 021308-000220PC) filed Dec. 10, 2004,which in turn claimed priority to U.S. Provisional Patent ApplicationSer. No. 60/529,325 filed Dec. 11, 2003; U.S. Provisional PatentApplication Ser. No. 60/615,117 filed Sep. 30, 2004; U.S. ProvisionalPatent Application Ser. No. 60/616,706 filed Oct. 6, 2004; and U.S.Provisional Patent Application Ser. No. 60/624,427 filed Nov. 1, 2004;the disclosures of which are herein incorporated by reference.

BACKGROUND OF THE INVENTION

Monitoring pressures and pressure changes in a human body is often animportant component of a medical or surgical diagnosis or therapy. Forexample, pressure changes in various body chambers, such as bloodpressures in chambers of the heart, may be used for diagnosis and/ortreatment of a number of conditions. One or more pressure sensorspositioned in a heart chamber, for example, may allow a physician tomonitor the functional ability of the heart to pump blood, such as in apatient suffering from congestive heart failure. Blood pressuremonitoring in the heart may also be used to automatically activate oradjust a pacemaker, such as a rate-responsive or pressure-responsivepace maker. In some cases, one or more pressure sensors may be implantedin a heart to sense chamber pressures over an extended time period andadjust pacemaker timing or the like. Both rate-responsive pacemakers andtechniques for measuring intracardiac pressures are known in the art.

Other bodily pressures and pressure changes may also be used in medicaland surgical diagnosis and treatment. Pressure changes across variousvalves or sphincters, within body chambers or tracts such as thedigestive tract, bladder filling and voiding pressures, and the like maybe sensed and measured for use in a medical or surgical context.

An ideal medical pressure sensor would be both very sensitive and verystable (i.e., having very limited drift over time), while also beingrelatively small. Some medical pressure sensing devices, for example,should be small enough to be conveniently implanted at a desired site ina patient or to be carried on a catheter.

Advances in micromachined sensor technology have been made in order todevelop small pressure sensing devices. Micromachined sensors typicallymeasure an environmental variable, such as a pressure or acceleration,by detecting the strain induced on a sensor element, i.e., transducer.The sensor converts the strain into an electrical signal by measuringthe resistance of the strained element, such as is done inpiezoresistive-based sensors, or the change in vibrational frequency ofthat element, such as is done in resonance-based sensors. Specifically,pressure sensors detect the strain in a diaphragm that is distended inresponse to a pressure change, while accelerometers measure the straincaused by the displacement of a proof mass under an inertial load.

Piezoresistive pressure sensors make up the bulk of commerciallyavailable microfabricated pressure sensors. In general, this type ofsensor uses two piezoresistors positioned on a circular or rectangulardiaphragm to form a 90 degree angle. FIGS. 1 and 1B, for example, show aprior art microfabricated pressure sensor 10 having a circular diaphragm12 with a radially oriented piezoresistor 16 and a circumferentiallyoriented piezoresistor 14. The two resistors 14, 16 are connected at onepoint to an output 17 of the sensor 10. The other two ends of theserially-connected resistors 14, 16 are connected to either voltage 13or ground 15. When the trans-membrane pressure of such a diaphragmincreases, the resistance of one of the resistors increases, and theother decreases. The effectiveness of the chip is adversely effected,however, by the fact that one resistance also increases and the otherdecreases when force is applied to the chip as a whole, such as bending,stretching and twisting forces. The sensitivity to such forces on thechip is inversely related to chip dimensions, so that the smaller thechip, the more sensitive it is to forces exerted on the chip. Such chipsmay be referred to as “single-point” sensors, in that they sense forcesat essentially one location on a diaphragm.

In an improvement over single-point sensors, some currently availablesensors include two resistors located along the perimeter of a diaphragmat separate locations, as shown in FIG. 1A. In this pressure sensor 10a, the radially oriented piezoresistor 16 a and the circumferentiallyoriented piezoresistor 14 a are distanced approximately ninety degreesapart along the perimeter of the diaphragm 12 a. Thus, sensor 10 a mayhave reduced sensitivity to stretching and bending, since thepiezoresistors 14 a and 16 a cancel each other out somewhat. However,such a sensor 10 a is equally sensitive to twisting forces as the sensor10 shown in FIG. 1, because twisting is sensed by the piezoresistors 14a, 16 a as pressure against the diaphragm 12 a.

Over extended periods of use, currently available pressure sensorsexperience drift. Drift is the distorting changes to base line readingswhich occurs as a result of a number of ambient factors. Drift normallyoccurs over time in pressure sensors. The variable quality of baselinesensor data drift in the sense of output interferes with obtaining datawhich accurately reflects changes in physiologic parameters. Driftobscures accurate data both by producing false positive and falsenegative readings. By example, false negative results can occur whendrift of base-line data readings distorts or fully obscures physiologicparameter changes in signal which would otherwise be indicative of adisease state. This occurs when the drift brings a “0” base line levelinto a negative range. Conversely, when sensor drift is in a positiverange it can be mistaken for a change in biological parameters, runningthe risk of a false indication of a disease state. Unfortunately, driftis typically unpredictable, and so can not be simply factored out ofcalculations in order to compensate for these data distortion.

It is a requirement for implantable pressure sensors that they have verystable output. This quality is necessary to assure that the datareadings from the sensors are a true reflection of the pressure thatthey are designed to measure. The drift characteristic of many pressuresensors can be problematic with implanted sensors, where recalibrationopportunities are limited or impractical. Because of the limited abilityto recalibrate implanted sensors, the failure of currently availablepressures sensors to remain stable (i.e., free of drift) in base-linedata output has made them unsuitable for long term implantable use.

It would be an important advancement in the art if a micromachinedpressure sensor were available that was resistant to drift in order tomake the many advantages of micromachined sensors available for longterm implantation applications by researchers and clinicians.

Relevant Literature.

Methods for pressure-modulated rate-responsive cardiac pacing aredescribed in U.S. Pat. No. 6,580,946. Techniques for monitoringintra-cardiac pressures are described in U.S. Pat. Nos. 5,810,735,5,626,623, 5,535,752, 5,368,040, 5,282,839, 5,226,413, 5,158,078,5,145,170 and 4,003,379.

BRIEF SUMMARY OF THE INVENTION

Implantable pressure sensors and methods for making and using the sameare provided. A feature of embodiments of the subject pressure sensorsis that they are low-drift sensors. The subject sensors find use in avariety of applications.

Embodiments of the subject invention provide physiological pressuresensor structures that include: a substrate; a compliant member mountedon the substrate in a manner such that the compliant member has firstand second opposing exposed surfaces; and at least one strain transducerassociated with a surface of the compliant member. In these embodiments,the pressure sensor structure is a low-drift pressure sensor structure.

In certain embodiments, the substrate includes an opening and thecompliant member spans the opening. In certain embodiments, thestructure includes at least first and second strain transducers mountedon a surface of the compliant member. In certain embodiments, the firstand second strain transducers are piezoresistors. In certainembodiments, the piezoresistors are fabricated from a high gaugematerial, e.g., a material comprises platinum (e.g., pure platinum, aplatinum alloy, etc). In certain embodiments, compliant member comprisessingle crystal silicon.

In certain embodiments, the first and second strain transducers arepositioned on a surface of the compliant member so that their outputsrespond oppositely to deflection of the compliant member resulting fromdifferential pressure across the compliant member but respond similarlyto deformation of said substrate. In certain embodiments, the first andsecond strain transducers are positioned on the same surface of thecompliant member. In certain embodiments, the first and second straintransducers are positioned symmetrically on the same surface on oppositesides of a line of symmetry. In certain embodiments, the structuresfurther include a boss on a surface of the compliant member. In certainembodiments, the first and second strain transducers are positionedadjacent to each other on a surface of the compliant member on one sideof a line of symmetry.

In certain embodiments, the first and second strain transducers arepositioned on opposing surfaces of the compliant member. In certainembodiments, the first and second strain transducers are directlyopposed to each other.

In certain embodiments, the compliant member is positioned at leastproximal to the structure's neutral plane.

In certain embodiments, at least one strain transducer is separated fromthe surface of said compliant member by a spacer. In certain of theseembodiments, the spacer separates said sensor from said compliant memberby a distance ranging from about from about 1 to about 1,000 μm.

Also provided are systems that include the subject sensor structures,where the systems are characterized by the presence of at least oneconductive member, e.g., a wire, operatively coupled to the transducerelements of the sensor structure. In certain embodiments, the systemincludes a plurality of the physiological pressure sensors operativelycoupled to said conductive member. In certain embodiments, the systemfurther includes an energy source coupled to said conductive member. Incertain embodiments, the system further includes a processing elementfor determining pressure changes in a volume in response to outputsignals from said transducer. In certain embodiments, the system isconfigured to be implanted into a patient. In certain embodiments, thesystem is configured so that the sensor is positioned on a heart wallupon implantation into a patient.

Also provided are methods for fabricating a pressure-sensor structure ofthe subject invention. In certain embodiments, the methods include:

-   -   positioning a layer of a compliant material on a surface of a        first substrate;    -   producing at least one strain sensor on a first surface of said        compliant material opposite said substrate;    -   producing a second substrate layer on said first surface of said        compliant member, such that said strain sensor layer is        interposed between said compliant member layer and second        substrate layer, wherein at least a portion of said compliant        member is exposed; and    -   producing a passageway in said substrate in a manner to expose a        second surface of said compliant member opposite said first        surface.

In certain embodiments, the method further includes producing a bossmember on said first surface of said compliant layer. In certainembodiments, the first and second substrates are configured such thatthe compliant member is positioned at least proximal to said structure'sneutral plane. In certain embodiments, the method is a method ofproducing a low drift physiological pressure sensor. In certainembodiments, the method further includes coupling the structure to aconductive member.

Also provided are methods for detecting a pressure change in a volume.The subject methods include contacting a pressure sensor structureaccording to the present invention with the volume; obtaining an outputsignal from the pressure sensor; and using the output signal to detect apressure change in the volume.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a top-view diagram of a prior art pressure sensor;

FIG. 1A is a top-view diagram of an alternative prior art pressuresensor

FIG. 1B is a side-view diagram of a prior art pressure sensor;

FIGS. 2A, 2B & 2C are side-view diagrams of various embodiments ofimproved piezoresistive pressure sensors according to variousembodiments of the present invention;

FIG. 2D is a top-view diagram of a diaphragm of a sensor structureaccording to an embodiment of the present invention;

FIG. 2E is a top-view diagram of a sensor structure according to anembodiment of the present invention;

FIG. 3 provides a plan view of a device according to another embodimentof the present invention;

FIG. 4 provides a view of an embodiment of the pressure sensor devicewith four piezoresistors;

FIG. 5 provides an alternate embodiment with a different arrangementdesign for the four piezoresistor elements;

FIG. 6 provides a circuit diagram of a representative embodiment of thepresent invention with electrically connected piezoresistors;

FIG. 7 provides a variation of the embodiment shown in FIG. 6;

FIGS. 8A & 8B provide a view where the piezoresistors are placed on topof a boss layer;

FIGS. 9A, B & C provide a view where the piezoresistors are placed bothunder and on top of a boss layer;

FIG. 10 provides a circuit diagram of an embodiment of the presentinvention;

FIG. 11 provides a cross-sectional view of an embodiment of the presentinvention;

FIG. 12 provides a circuit diagram of an embodiment of the presentinvention;

FIG. 13 provides a cross sectional view of one embodiment of theinventive pressure sensor device;

FIGS. 14A & B provide cross sectional and planar views of a prior artpressure sensor;

FIGS. 15A & B provide cross sectional and planar views of a prior artpressure sensor experiencing a bending stress;

FIGS. 16A & B provide cross sectional and planar views of a prior artpressure sensor experiencing an opposite bending stress;

FIGS. 17A & B provide cross sectional and planar views of the inventivesensor device with the sensor element located at or near the neutralplane of the device;

FIGS. 18A & B provide cross sectional and planar views of the device inFIGS. 17A & B experiencing a bending stress in a direction away fromsensor diaphragm;

FIGS. 19A & B provide planar and cross sectional views of the inventivedevice shown in FIGS. 17A & B with a stress of the opposite magnitudeapplied to the chip from that in FIGS. 18A & B;

FIGS. 20A & B provide cross sectional and planar views of yet anotherrepresentative embodiment of the present invention;

FIGS. 21A & B provide cross sectional and planar views of yet anotherrepresentative embodiment of the present invention;

FIG. 22 provides a cross sectional view of a prior art pressure sensingdevice;

FIG. 23 provides a cross sectional view of an embodiment of the presentinvention;

FIG. 24 provides a cross sectional view of an alternate embodiment ofthe present invention;

FIG. 25 provides a view of an inventive in-plane and mechanicalamplification;

FIG. 26 provides a diagrammatic view of one embodiment of the presentinvention;

FIG. 27 is a circuit diagram of a basic pressure sensing circuit whichmay be used in various embodiments of the present invention;

FIG. 28 is a circuit diagram of a six-wire circuit which may be used invarious embodiments of the present invention;

FIG. 29 is a circuit diagram of a compensating pressure sensing circuitwhich may be used in various embodiments of the present invention;

FIG. 30 is a circuit diagram of an alternative embodiment of acompensating pressure sensing circuit which may be used in variousembodiments of the present invention;

FIG. 30A is a circuit diagram of a VCDCO circuit which may be used invarious embodiments of the present invention;

FIGS. 30B & C provide circuit diagrams of alternative embodiments of thepresent invention;

FIG. 30D provides a diagram showing an alternate circuitry component;

FIGS. 31A to 31U are diagrams showing a method for microfabricating amedical pressure sensor according to one embodiment of the invention;

FIGS. 32A to 32G are diagrams showing a method for microfabricating apressure sensor according to another embodiment of the invention;

FIG. 33 provides a flow diagram for a method of fabricating a sensorstructure having a sensor element(s) positioned at least proximal to theneutral plane of the sensor structure;

FIGS. 34A to 34H are diagrams showing a method for microfabricating apressure sensor according to one embodiment of the invention; and

FIGS. 35A to F are diagrams showing a method for microfabricating apressure sensor according to one embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

Low-drift implantable pressure sensors and systems including the same,as well as methods of making and using the same, are provided. Thesubject sensors are characterized by having at least a substrate, acompliant member mounted on the substrate in a manner such that thecompliant has first and second exposed surfaces, and at least one straintransducer associated with a surface of the compliant member. A featureof the subject devices is that they exhibit low-drift. The subjectdevices and methods find use in a variety of different applications.

Before the present invention is further described, it is to beunderstood that this invention is not limited to particular embodimentsdescribed, as such may, of course, vary. It is also to be understoodthat the terminology used herein is for the purpose of describingparticular embodiments only, and is not intended to be limiting, sincethe scope of the present invention will be limited only by the appendedclaims.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range, is encompassed within the invention. The upper and lowerlimits of these smaller ranges may independently be included in thesmaller ranges and are also encompassed within the invention, subject toany specifically excluded limit in the stated range. Where the statedrange includes one or both of the limits, ranges excluding either orboth of those included limits are also included in the invention.

Methods recited herein may be carried out in any order of the recitedevents which is logically possible, as well as the recited order ofevents.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can also beused in the practice or testing of the present invention, the preferredmethods and materials are now described.

All publications mentioned herein are incorporated herein by referenceto disclose and describe the methods and/or materials in connection withwhich the publications are cited.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “an”, and “the” include plural referents unless thecontext clearly dictates otherwise. It is further noted that the claimsmay be drafted to exclude any optional element. As such, this statementis intended to serve as antecedent basis for use of such exclusiveterminology as “solely,” “only” and the like in connection with therecitation of claim elements, or use of a “negative” limitation.

The publications discussed herein are provided solely for theirdisclosure prior to the filing date of the present application. Nothingherein is to be construed as an admission that the present invention isnot entitled to antedate such publication by virtue of prior invention.Further, the dates of publication provided may be different from theactual publication dates which may need to be independently confirmed.

As summarized above, the subject invention provides implantable pressuresensors, as well as methods for their preparation and use. In furtherdescribing the subject invention, the subject sensors and theirpreparation are described first in greater detail, followed by a reviewof representative methods in which they find use. Also provided is areview of the kits and systems of the subject invention.

Implantable Pressure Sensors

As summarized above, the present invention provides implantable pressuresensors. The implantable pressure sensors are sensors that may bepositioned in or on a body and function without significant, if any,deterioration for extended periods of time. As such, once implanted, thesubject sensors do not deteriorate in terms of function for a period ofat least about 2 or more days, such as at least about 1 week, at leastabout 4 weeks, at least about 6 months, at least about 1 year or longer,e.g., at least about 5 years or longer.

In certain embodiments, the subject sensors do not functionallydeteriorate because they exhibit low drift. As such, a feature of manyembodiments of the subject invention is that that the sensor structuresexhibit low drift, i.e., they are low-drift pressure sensors. Sensors ofthese embodiments have relatively high sensitivity and stability (i.e.,low drift). In one embodiment, for example, the sensor device maymeasure pressure changes in a volume, (i.e., an ambient), with a driftof no more that about 1.0 mmHg per year. For the purposes of thisapplication, “a volume” means any space, chamber, cavity, substance,tissue, area or the like. In some instances a volume will comprise achamber of a human body, such as a heart chamber, but this is only oneexample of a volume, and the invention is in no way limited by thisexample. For example, in various embodiments a volume may be a space,cavity or the like that is not in a human body, and sensors of thepresent invention may be used in a wide variety of non-medical contexts.Therefore, although the following discussion generally focuses onsensing pressure changes in human heart chambers, the invention is in noway limited to such an application.

In certain embodiments, the subject pressure sensors exhibit little orno drift over a period of from about 1-40 years, such as from about 5-35years, and including from about 5-30 years. The drift diminutionachieved by these embodiments is about 10-400%, most preferably 40-350%,and most preferably 50-300%, as compared to the prior art structureshown in FIGS. 1 to 1B.

Drift rates of a given sensor structure may be determined by monitoringthe output of the sensor vs. time when the device is employed in atypical use environment, or model thereof. In such tests, drift may beassessed by maintaining pressure at a stable value, e.g., constantvalue, and monitoring the output of the sensor over time in order toascertain any changes in the output, which are then employed todetermine the drift of the device.

The drift test that is employed may be one that accelerates the driftprocess beyond that which occurs naturally in an in situ environment,e.g., so as to provide for the acquisition of useful data withoutrequiring waiting for the full lifetime of a sensor to pass. There arevarious methods that can be employed to accelerate the external,challenging factors which result in pressure sensor drift. The simplestway to accelerate drift is to elevate the temperature to which thesensor is subject. It is conventional in the art that, for every tendegree centigrade increase in temperature beyond the intendedtemperature of sensor use, the observed drift will increase by a factorof two. For example, if drift is monitored at a temperature of 50° C.higher than the intended operating temperature, a 32-fold accelerationin the drift is observed. As a result, in this accelerated driftenvironment, for every day of observation, the device would experiencethe same amount of drift that would normally be experience in 32 days atthe normal operating temperature. As such, drift assays that may beemployed include increased temperature drift assays.

When the specific cause of the drift can be identified, driftacceleration tests can be tailored to evaluate the sensor response dueto that specific cause. By example, if the fundamental source of driftis due to a mismatch in the thermal expansion coefficient of thedifferent materials that make up the sensor, drift can be accelerated bychanging the temperature. This would also be the case where drift wasdue to material differences between the sensor and the packaging inwhich the sensor resides. Specifically, drift due to mismatched thermalexpansion coefficients can be evaluated by cycling the temperaturebetween −5° C. and 95° C., e.g., for about 5, 10 or 50 or more cycles.This evaluation process, when accomplished, while monitoring the output,will give an indication of the stability of the sensor and its immunityto drift from thermal expansion mismatch sources.

A fundamental cause of a drift is mechanical stress. Mechanical stressis due to such factors as the bending of the package on which the sensoris placed. To evaluate an accelerated test of drift, a fixture isdesigned that applies a known mechanical deformation to the sensor. Theoutput is then monitored to evaluate the accelerated drift rate. Byexample, a three-point bending test fixture can be usefully employed inthis manner. Similarly, if the fundamental cause the drift is chemicalin nature, the drift can be accelerated by exposing the sensor to achemical environment that is harsher than the normal operatingenvironment. By example, if the major source of drift is caused bycorrosion due to saline, one can place a sensor in a concentrated salinesolution and monitor the output. Where multiple factors effecting driftare major players in the overall drift rate, it will in some cases beuseful to combine several methods of testing, such as those describedabove. Also, adding additional challenging factors can be used tofurther accelerate the effect of a single faction. By example, thesensor to be tested can be challenged by being placed in a salineenvironment, and then adding an additional challenging factor byelevating the temperature. This approach would both accelerate salineinduce corrosion of the sensor, as well as accelerate material fatigue.

Whatever drift test is employed, where in certain embodiments a drifttest as described above is employed, as sensors according to the subjectinvention are low-drift, they will exhibit drift, if at all, of fromabout 1 mm Hg/day to about 1 mm Hg/20 years, such as from about 1 mmHg/week to about 1 mm Hg/10 years, including from about 1 mm Hg/month toabout 1 mm Hg/7 years, e.g., from about 1 mm Hg/year to about 1 mm Hg/5years. This low drift characteristic of the subject sensors is in sharpcontrast to the drift observed in many current prior art pressuresensors, where the observed drift may be 7 mmHg/hr.

In certain embodiments, the implantable sensors may be characterized asphysiologic. The phrase “physiologic” as employed herein denotes thatthe sensors are configured (e.g., shaped, dimensioned etc.) so that theycan be positioned in or on a body of a living organism, such as amammal, e.g., a human. In representative embodiments, sensor structuresof the present invention are small enough to be conveniently implantablein a human body (and/or coupled with a catheter). In certainembodiments, the devices are configured as a rectangular chip having alength along an edge of the chip of no more than about 500 μm and atotal thickness of no more than about 100 μm.

The sensors of the subject invention generally include a substantiallyplanar substrate and a compliant member mounted on a surface thereof,i.e., positioned or disposed on a surface thereof. The compliant memberis generally a planar structure mounted on the substrate in a mannersuch that opposing planar surfaces of the compliant member are exposed,i.e., not touching the substrate surface on which the compliant memberis mounted. As such, at least a portion of the top and bottom planarsurfaces of the compliant member are not touching the substrate, eventhough the compliant member is mounted on the substrate. In addition,the subject sensor structures typically include at least one straintransducer associated with at least one surface of the compliant member,typically an exposed surface of the compliant member. By “associatedwith” is meant that the transducer is mounted on the compliant membersurface, either directly or through a spacer element. As furtherelaborated below, the number of transducers that may be present on thecompliant member may vary from one to a multitude thereof. Additionalfeatures of different embodiments of the subject sensors are furtherreviewed below.

In some embodiments, the device measures pressure changes in a volumewith a sensitivity of about +/−1 mmHg on a scale of about 500-1000 mmHg.

In certain embodiments, the subject sensors structures have one or moreof the following features, including two or more, three or more, four ormore, as well as all of the following features, to the extent suchfeatures are compatible in a single sensor structure. In certainembodiments, a feature of the sensor structures is that theconfiguration of the sensor transducers is such as to provide for thelow-drift characteristic. In certain embodiments, a feature of thesensor structures is that the materials employed for the differentcomponents of the structure are specifically chosen to provide for thelow-drift characteristic. In certain embodiments, a feature of thesensor structure is that the compliant member of the structure ispositioned at least proximal to the neutral plane of the structure so asto provide for the low drift characteristic. In certain embodiments, afeature of the sensor structure is that the sensor element(s) (i.e.,transducer) is separated from the compliant member surface with which itis associated by a spacer element, e.g., to enhance a signal to noiseratio. Each of the above features is now described in greater detailbelow.

Low-Drift Sensor Component Configurations

As summarized above, in certain embodiments the subject sensorstructures have a component configuration that imparts a low-driftcharacteristic to the sensor structure. In these embodiments, the sensorstructures typically include a substrate, also referred to herein as achip or support structure. The substrate is generally a rigid structure,where in representative embodiments, the structure has dimensions toprovide for sensor structures of a size described above. In manyembodiments, the substrate includes a passage, which may be incomplete(such as a well configuration) or complete (such as a holeconfiguration).

Mounted on the substrate is a compliant member, where the term“compliant member” is used interchangeably with membrane and diaphragm.The compliant member is a flexible structure that deforms in response topressure differentials applied across the compliant member. As such, thecompliant member is an elastic material. In certain embodiments, thecompliant member has a thickness ranging from about 0.1 to about 100micrometers, such as from about 0.5 to about 10 micrometers, includingfrom about 1 to about 5 micrometers. In certain embodiments, thecompliant member spans the passage of the substrate, so as to produce astructure in which a pressure differential across the compliant membermay be produced.

Associated with at least one surface of the compliant member is at leastone strain transducer, where the phrase “strain transducer” means anydevice that is capable of transforming mechanical energy produced bydeformation of the compliant member, e.g., in response to a pressuredifferential imposed across the compliant member, into electricalenergy. The phrase “strain transducer” is used interchangeably with thephrase sensor element, and may be any kind of strain transducer,including piezoresistor, vibrational, and the like, as is known in theart.

The transducers may be positioned at any of a number of suitablelocations on the diaphragm, and any suitable number, shape and/or sizeof transducers may be used.

In certain embodiments, the sensor structures include at least a firstand second strain transducer. A feature of these representativeembodiments is that the first and second strain transducers, e.g.,piezoresistors, are positioned in the device so as to respond equally toforces, moments and torques applied to the substrate and respond equallyand oppositely to changes in pressure in the volume, to allow formeasurement of the pressure changes with limited interference from theforces, moments and torques applied to the substrate. For example, theforces, moments and torques may generally include bending, twistingand/or stretching.

In these representative embodiments, the transducers on the sensorstructure respond differently to deflection of the diaphragm caused bypressure changes in the volume than they do to forces, moments andtorques applied to the substrate. These forces, moments and torques,which may be referred to as “artifact,” reduce the accuracy of a sensordevice, especially over time. Examples of artifact forces which mayaffect performance of sensor structure include twisting, stretching,bending, compression, strain and the like. Transducers, e.g.,piezoresistors, of “multiple-point” sensors of the present invention, incontrast to those of conventional single-points sensors, are configuredto respond relatively equally to pressure changes in a volume whileresponding equally and oppositely to forces, torques and moments appliedto the substrate. By “equally,” it is meant at least relatively orapproximately equally. When the piezoresistors are arranged in series,this response causes pressure changes in the volume to be sensedcumulatively by pairs of piezoresistors while forces, moments andtorques are canceled out. By reducing the sensitivity of the sensor tomechanical forces and moments applied to the sensor chip, long termdrift is drastically reduced.

As such, the transducers of these embodiments are associated with thesurface of the compliant member so that their outputs responseoppositely to deflection of the compliant member resulting fromdifferential pressure across the compliant member, but respond similarlyto deformation of the substrate.

In one aspect of this embodiment of the present invention, a sensorstructure includes: a substrate; at least one compliant member, i.e.,diaphragm or membrane, mounted on the substrate and having a firstsurface exposed to a volume and a second opposite surface exposed to anenclosed space; a first strain transducer, e.g., piezoresistor, disposedon the first surface; and at least a second strain transducer, e.g.,piezoresistor, disposed on the second surface directly opposite thefirst piezoresistor and coupled with the first piezoresistor in series.

For purposes of further description only, the subject invention will bedescribed in terms of embodiments where the strain transducers arepiezoresistors. However, it should be noted that other types of straintransducers are contemplated, including those mentioned above, and suchalternative transducers are in no way excluded from the scope of theinvention simply by further describing the invention herein in terms ofpiezoresistive transducer embodiments.

In certain embodiments, the first and second piezoresistors may bedisposed near a center of the compliant member, i.e., diaphragm ormembrane. In some embodiments, the diaphragm may further include athicker region, e.g., the form of a boss or analogous structure, at thecenter on at least one of the first and second surfaces. This region mayserve as a stress-focusing member. In these embodiments, the first andsecond piezoresistors may be disposed adjacent the thicker region.Optionally, the thicker region may comprise a circular region ofincreased thickness on both the first second surfaces.

Some embodiments of the sensor device may further include a thirdpiezoresistor positioned near an edge of the compliant member, e.g.,diaphragm on the first surface of the diaphragm and at least a fourthpiezoresistor positioned near the edge of the diaphragm on the secondsurface, directly opposite the third piezoresistor and coupled with thethird piezoresistor in series. The third and fourth piezoresistorsrespond equally to forces, moments and torques applied to the substrateand respond equally and oppositely to changes in pressure in the volume,to allow for measurement of the pressure changes with limitedinterference from the forces, moments and torques applied to thesubstrate. In some embodiments, these first, second, third and fourthresistors comprise a Wheatstone Bridge. The sensor device may optionallyfurther include a plurality of additional piezoresistors disposed alongthe diaphragm such that each piezoresistor disposed near the edge of thediaphragm is matched with a piezoresistor disposed adjacent the thickerregion of the diaphragm. In some cases, the additional piezoresistorsare disposed around the entire circumference of the edge of thediaphragm and around the entire circumference of the thicker region onat least one surface of the diaphragm.

In another aspect of the invention, a sensor structure includes: asubstrate; at least one diaphragm mounted on the substrate and having afirst surface exposed to a volume and a second opposite surface exposedto an enclosed space; a first piezoresistor disposed near an edge of thediaphragm on the first surface; and at least a second piezoresistordisposed near a center of the diaphragm on the first surface, in radialalignment with and coupled in series with the first piezoresistor.Again, the first and second piezoresistors respond equally to forces,moments and torques applied to the substrate and respond equally andoppositely to changes in pressure in the volume, to allow formeasurement of the pressure changes with limited interference from theforces, moments and torques applied to the substrate.

Some embodiments may further include a third piezoresistor positionednear the edge of the diaphragm on the second surface of the diaphragm,directly opposite the first piezoresistor, and at least a fourthpiezoresistor positioned near the center of the diaphragm on the secondsurface, directly opposite the second piezoresistor and coupled with thethird piezoresistor in series. The third and fourth piezoresistorsrespond equally to forces, moments and torques applied to the substrateand respond equally and oppositely to changes in pressure in the volume,to allow for measurement of the pressure changes with limitedinterference from the forces, moments and torques applied to thesubstrate. Sensors according to this aspect of the invention may haveany of the characteristics described above.

In one embodiment, a first plurality of piezoresistors is disposedcircumferentially around at least a part of the edge of the diaphragm onthe first surface, and a second plurality of the piezoresistors isdisposed circumferentially around at least part of the first surface ofthe diaphragm closer to its center than the first plurality. In thisembodiment, each piezoresistor of the first plurality is electricallycoupled in series with one piezoresistor from the second plurality.

In certain embodiments, a first elongated piezoresistor is disposedcircumferentially around at least part of the edge of the diaphragm onthe first surface, and a second elongated piezoresistor is disposedcircumferentially around least part of the diaphragm on the firstsurface, closer to the center than the first piezoresistor and coupledin series with the first piezoresistor. These and other embodiments mayfurther include piezoresistors disposed on the second surface of thediaphragm as well as the first, and such further piezoresistors mayoptionally be coupled with the first and second piezoresistors inparallel.

Representative configurations of these embodiments are now furtherdescribed in terms of the figures. FIGS. 2A to 2C are schematic sideviews of implantable medical pressure sensors according to variousembodiments of the present invention. As with all figures in thisapplication, these drawing figures are not necessarily drawn to scale,but are provided for explanatory purposes only. With reference to FIG.2A, a sensor device 20 includes a substrate 29, a diaphragm 22 mountedon substrate 29, a first piezoresistor 24 located on a first surface 23of diaphragm 22, and a second piezoresistor 26 located on a secondsurface 25 of diaphragm 22 directly below first piezoresistor 24. Firstsurface 23 is exposed to a volume A, while second surface 25 is exposedto an enclosed space 21. The large, hollow arrows in FIG. 2A demonstratestretching and bending forces which may be placed on the substrate 29.The positions of first piezoresistor 24 and second piezoresistor 26generally allow them to respond equally to such bending and stretching,as well as other forces, moments and torques applied to the substrate,while responding equally and oppositely to changes in pressure in thevolume, to allow for measurement of the pressure changes with limitedinterference from the forces, moments and torques applied to thesubstrate.

Referring now to FIG. 2B, another embodiment of a sensor device 30includes a substrate 39, a diaphragm 32 mounted on substrate 39, a firstpiezoresistor 36 located near the edge of diaphragm 32 and a secondpiezoresistor 34 located near the center of diaphragm 32. Suchpiezoresistors may be either on a second surface 33, exposed to anenclosed space 31 (as shown in the figure), or on a first surface 37 ofdiaphragm 32, exposed to a volume A. Some embodiments may also include acentral “boss” or thicker region 35. Thicker region 35 may extend fromfirst surface 37 (as in FIG. 2B), second surface 43, or both (as in FIG.2C). Generally, thicker region 35 enhances the ability of first andsecond piezoresistors to respond equally to forces, moments and torquesapplied to the substrate and respond equally and oppositely to changesin pressure in the volume, to allow for measurement of the pressurechanges with limited interference from the forces, moments and torquesapplied to the substrate.

With reference now to FIG. 2C, another embodiment of a sensor device 40includes a substrate 49, a diaphragm 42, and four piezoresistorsdisposed on diaphragm 42: a first piezoresistor 44 a located on a firstsurface 47 near the center of diaphragm 42; a second piezoresistor 44 bon a second surface 43 near the center of diaphragm 42; a thirdpiezoresistor 46 a on first surface 47 near the edge of diaphragm 42;and a fourth piezoresistor 46 b on second surface 43 near the edge ofthe diaphragm 46 b. In such embodiments, the fours piezoresistors 44 a,44 b, 46 a, 46 b may comprise a full Wheatstone bridge.

Referring now to FIG. 2D, in one embodiment a diaphragm 57 of a sensordevice includes a first plurality of piezoresistors 56, a secondplurality of piezoresistors 54, a central thicker region 55, an output52, a ground 51 and a voltage 53. The first plurality 56 is disposedcircumferentially around the edge of diaphragm 57, extending completelyor almost completely around diaphragm 57 (as designated by dottedlines). The second plurality 54 similarly extends circumferentiallyaround diaphragm 57, but is disposed closer to the center, adjacentthicker region 55. In this embodiment, each piezoresistor of the firstplurality 56 is coupled in series with the piezoresistor of the secondplurality 54. In some embodiments, third and fourth pluralities ofpiezoresistors may be disposed on the surface of diaphragm 57 oppositethe surface shown, and the first and second pluralities may be coupledwith the third and fourth pluralities in parallel.

In an alternative embodiment, and with reference now to FIG. 2E, adiaphragm 67 of a sensor device may include a first elongatedpiezoresistor 66 disposed near the diaphragm edge and a second elongatedpiezoresistor 64 disposed closer to the diaphragm center, adjacent athicker region 65. The diaphragm 67 may further include an output 62, aground 61 and a voltage 63. Again, additional elongated piezoresistorsmay be disposed on an opposite side of diaphragm 67 and may be coupledwith the first and second piezoresistors 64, 66 in parallel. From theexamples shown in FIGS. 2A to 2E, it should be apparent that any numberand configuration of piezoresistors may be used in a given embodiment ofa sensor device without departing from the scope of the presentinvention.

Sensor structures of the present invention may have any suitable numberof diaphragms and any suitable number of piezoresistors disposed on eachdiaphragm. For example, in some embodiments, piezoresistors may bedisposed along the entire outer circumference, inner circumference, orboth, of a diaphragm. Such circumferential piezoresistors may be on afirst surface, a second surface, or both. Typically, each piezoresistordisposed on a diaphragm will correspond with another piezoresistor,either radially positioned on the same surface or disposed directlyopposite the piezoresistor on the opposite surface of the diaphragm.Diaphragm(s) on a sensor device, furthermore, may have any suitableshape, size, thickness or the like. Although circular diaphragms areshown, for example, any other size may be used.

As mentioned above, some embodiments (FIGS. 2B and 2C, for example)include a thicker region-at the center of the diaphragm. Such a regionmay include increased thickness on a first surface of the diaphragm, asshown in FIG. 2B, increased thickness on a second surface, or increasedthickness on both, as shown in FIG. 2C. Such a thick region or boss actsto increase the stiffness of the diaphragm without increasing its outerdimensions. In some embodiments, also as shown in FIGS. 2B and 2C, oneor more piezoresistors may be positioned near such a thickened region.

Pressure sensors 20, 30, 40 may have any suitable size, shape andconfiguration and may be made of any suitable materials. In someembodiments, for example, an implantable pressure sensor device measuresabout 100-500 μm on an edge and less than about 100 μm thick. Thesubstrate may be made of silicon and/or other materials which may bemicrofabricated. In some embodiments, the piezoresistors are made ofplatinum, though other materials such as polysilicon or single-crystalsilicon may be used, as described in greater detail below. As indicatedabove, the sensor is fabricated to have a high sensitivity andstability. In one embodiment, for example, the sensor has a sensitivityof about +/−1 mmHg absolute on a 500-1000 mmHg scale and a drift ofabout 1 mmHg/5 years. Other sensitivities and specificities are alsocontemplated within the scope of the invention, however.

FIG. 3 provides a plan view of a device according to anotherrepresentative embodiment of the invention. Pressure sensor chip 109 hasan opening on the back side 111. Piezoresistors 113 are proved in aserpentine pattern, covering the membrane area 115, and centered on themembrane boss area 117. In this embodiment, piezoresistors 113 areprovided as a single pair.

FIG. 4 shows an advantageous inventive design which goes beyond the twopiezoresistors embodiment shown in FIG. 3. In FIG. 4 is shown fourpiezoresistors, 119, 121, 123 and 125. These piezoresistor elements arearranged in such a way that the piezoresistors closest to the boss, thatis 119 and 123, will experience strain in one direction that is eithercompressive or tensile strain. By contrast, piezoresistors closest tothe edge of the membrane, piezoresistors 121 and 125, will experiencethe opposite strain.

FIG. 5 provides an alternate embodiment with a different arrangementdesign for four piezoresistors elements. In FIG. 5, piezoresistors 127and 129 are near the outside of the membrane, while piezoresistors 131and 133 are closer the center of the membrane. This embodiment performsthe same function as those inventive designs shown in FIGS. 3 and 4.However, the embodiment shown in FIG. 5 is less sensitive to fabricationtolerances.

FIG. 6 provides a representative embodiment of the present inventionwherein the piezoresistors are connected electrically. In this view,piezoresistor 135 and 137 are the piezoresistors closest to the boss,whereas piezoresistors 139 and 141 are closest to the edge of the sensormembrane. Supply voltage is applied to electrical terminals 143 and 145,while the output voltage is measured between terminals 147 and 149. Whenpressure is applied to the sensor membrane, the membrane will deform.This will, in turn, cause a stretching in the piezoresistors 135 and137, increasing their resistance. Compression in piezoresistors 139 and141 causes a decrease in their resistance.

In the Wheatstone bridge arrangement exemplified in this embodiment, thedecrease in resistance causes the voltage at terminal 147 to become morepositive than the voltage at terminal 149. By measuring the voltagebetween those two terminals, an increase in voltage is observed in theform of an electrical signal. This signal can be observed directly orprocessed by standard processing techniques to obtain digital data.

FIG. 7 provides a variation of the embodiment shown in FIG. 6. Pressuresensor membrane 151 is supported on substrate 153. Boss layer 155 ispatterned into a boss 153 in the center of the membrane 151, andadditionally forms rim 157 around the edge of the membrane 151. Thisembodiment of the present invention is advantageous for fabricationbecause the alignment of cavity 159 with respect to the features on thefront side, that is the boss layer 155 and piezoresistors 161, is lesscritical. Potential misalignment does not affect the pressure responsebecause the size of the membrane is effectively defined by rim 157.

An additional variation on this approach is shown in FIGS. 8A & 8B. Inthis embodiment, membrane 163 is a supported by wafer 165. A feature ofthis variant is that piezoresistors 167 are placed on top of boss layer169. FIG. 8B provides a plan view of the structure. Piezoresistor 167 issituated on top of the boss layer 169. In this case, the boss layer 169is patterned to accommodate and define the membrane edge 171, thepressure enhancing boss 173, and also the traces for the piezoresistor175.

By placing the piezoresistors 167 on top of the boss layer 169, a stressamplification effect is achieved, where the boss layer acts as spacer,as further described below. This effect is achieved because the strainmeasuring element, i.e., the piezoresistors 167, has been positionedfurther away from the neutral plane of the membrane, as is described inU.S. Patent Application No. 60/615,117 filed on Sep. 30, 2004,incorporated herein by reference as well as above, and described ingreater detail below.

The various concepts shown in the above figures are shown coordinated ina single device in FIGS. 9A, 9B & 9C. In these views, piezoresistors 177are situated underneath the boss layer. Additional piezoresistors 178are provided on top of the boss layer. FIG. 9A provides a planar view ofthis embodiment, while FIGS. 9B and 9C provide cross sectional views.The boss layer is patterned to define the edge of membrane 179, pressurefocusing boss 181, as well as a path for the top layer piezoresistor178. The bottom layer piezoresistor 177 is deposited and patternedunderneath the boss layer.

FIG. 10 provides a view of the electrical connections between theelements as show in FIGS. 9A to 9C. Piezoresistors 183 and 185 are thebottom layer piezoresistors, while piezoresistors 187 and 189 are thetop layer piezoresistors. When a voltage is supplied between terminals191 and 193, an output proportional to the pressure will be observedbetween terminal 195 and 197.

The advantage of the particular arrangement of FIG. 10 is demonstratedin FIG. 11. This figure is a schematic view of pressure sensor chip 199experiencing a bending stress that causes entire chip 199 to bend. Fromthis diagram, it can be observed that this bending stress will causepiezoresistors 201 and 203 to stretch. However, because of theelectrical configuration shown in FIG. 12, all four piezoresistors 205,206, 207, and 208, will experience the same bending stress. In this way,piezoresistors 205, 206, 207, and 208 will all increase in resistance,and there would be no net change in the voltage between terminals 209and 210. This figure demonstrates how this particular implementation isinsensitive to stress applied to chip 199.

Low-Drift Component Materials

As indicated above, in certain embodiments the various components of thesensor structures are fabricated from specific materials, as well ascombinations thereof, that impart low-drift characteristics to thesensor structures.

In certain embodiments, the sensor membrane is constructed of a verystable material, which is ideally purely elastic. In this manner,change, creep, or change in strain which typically occurs over time inprior art sensors are substantially limited, ideally eliminated, insensor membrane. The major design advancement is to assure that thepressure sensing elements, typically piezoresistors, are very stable, sothat their resistance undergoes very limited or no change over time.

One embodiment of the inventive pressure sensor device is shown in FIG.13, provided in cross section. A sensor membrane 101 is supported by asupport substrate 103, where sensor membrane 101 contains a stressfocusing boss 105, and pressure sensing elements 107. Pressure sensingelements 107 are typically resistors, particularly piezoresistors. Theresistance of pressure sensing elements 107 is a function of the appliedstress. As pressure is applied to sensor membrane 101, the membrane willdeflect. The deflection of sensor membrane 101 produces stress in thesensor membrane 101, and as a result in the associated pressure sensingelements 107. The stress on pressure sensing elements 107 causeelectrical resistance changes in pressure sensing elements 107,resulting in a measurable electrical signal related to the level ofapplied stress.

As an adjunct to the above teaching, in a representative embodiment ofthe present invention, both support substrate 103 and sensor membrane101 are made of single crystal silicon. The pressure sensing elements107 may be made of a stable gauge material, particularly a highlystable, e.g., a platinum comprising material, such as pure platinum oran alloy thereof; nickel chromium or alloys thereof; and the like.Alternatively, the pressure sensing elements 107 can be made ofpoly-crystalline silicon or similar materials.

In certain embodiments, the pressure sensor elements, e.g., platinumcomprising piezoresistors, have a passivating layer disposed on thesurface thereof. The passivating layer may range in thickness from about50 to about 100 nm, and may be of any convenient material, e.g., siliconnitride.

Stress focusing boss 105 can be effectively constructed from a number ofmaterials. However, preferably the materials for stress focusing boss105 is utilized that have a low stress and a similar thermal expansioncoefficient to the materials employed in sensor membrane 101. Ideally,materials for stress focusing boss 105 are selected from siliconnitride, poly-crystalline silicon, or amorphous silicon. These materialscan be deposited by any number of standard semi conductor applicationmethods discussed in more detail below.

Neutral Plane Embodiments

In certain embodiments, the compliant member, and therefore sensorelements associated with a surface thereof, of the subject devices arepositioned at least proximal to, i.e., at or near, the neutral plane ofthe pressure sensor structure or chip. In other words, embodiments ofthe present invention provide a sensor design in which the membrane inthe pressure sensor structure is situated in, adjacent to, through, ornear the neutral plane of the structure in which the compliant member ispresent. Once so designed, if the total pressure sensor structure, e.g.,chip, experiences bending stress, the compliant member will not bedistorted by that stress. The result of the inventive design is that thesensor element within the pressure sensor does not respond to backgroundstress, or responds only in an attenuated manner. Even partial adherenceto the present inventive teaching can mitigate response to backgroundstress at a level which substantially limits background pressurereadings. If a particular inventive design calls for positioning that isnot directly within the neutral plane, but none the less adjacent to orintersecting the plane, the distortion will be substantiallyameliorated. The present inventive design and fabrication method thusprovides a sensor with unprecedented stability.

The consideration of the neutral plane has previously been usefullyapplied in the engineering design of large, generally monolithic,objects such as solid beams and airplane wings. However, the inventionof these particular embodiments unexpectedly and innovatively appliesthe basic principle of the neutral plane to the unique environment ofmicromachined pressure sensor chips. This represents a sharp divergencefrom the prior application of the neutral plane guidelines toengineering designs, as micromachined pressure sensors have thechallenge of extremely small dimensions and often complex shapes,structures, and heterogeneous materials.

The inventive approach of specifically positioning a compliant memberand associated sensor element within the body of a pressure sensor chipin order to provide greater stability represents a sharp deviation frompresent fabrication techniques. For instance, it is currently standardpractice to produce sensing devices with the sensing element situated onthe outside surface of the larger sensing structure. While this standardfabrication method provides simplicity of construction, it positions thesensing element at the most extreme position possible from the neutralplane. The prior microsensor designs thus are at the most exaggeratedvulnerability to external forces. Thus, the teaching of the presentinvention results in sensor designs which are unique in the present art.

While unexpected in application to small, irregularly shaped devices asin the present invention, the basic understanding of the neutral planein other applications has been well established. The neutral plane issometimes described as the “neutral axis” plane. Descriptions andreviews of the neutral plane of objects, such as beams, is well known inthe art. See e.g., McMahon & Graham, “The Bicycle & the Walkman,” Merion(1992). See also http://darkwing.uoregon.edu/˜struct/courseware/461/461_lectures/461_lecture38/461_lecture38.html.As such, the concept of a structure's neutral plane is well known tothose of skill in the art. The neutral plane concept is furtherdescribed in priority U.S. Provisional Patent Application Ser. No.60/615,117 filed Sep. 30, 2004; the disclosure of which is hereinincorporated by reference.

Briefly, mechanical structures subject to bending stress have withinthem a theoretical plane that experiences pure bending. Other sectionsof this body will exhibit compression or tension in response to thebending stress. By example, typically the material above the neutralplane will experience tension if the bending stress is exerted in anupward direction. Conversely, the material below the neutral plane willtypically experience compression. However, materials in that neutralplane of the body will theoretically enjoy an absence of tension orcompression. In actual practice, due to the practical multidimensionalnature of secondary forces, there can be some stresses in some areas ofthe “neutral plane”. However, these stresses are much diminishedrelative to the other areas of the object.

Classically, for simple homogeneous solids, the neutral plane can becalculated from methods well know to the ordinary skilled engineer for asquare chip of uniform thickness and uniform material. In this case theneutral plane is at the geometric center of the object. For morecomplicated geometries, the neutral plane can, in some cases, becalculated from standard formulas.

While the present application uses the term “neutral plane” in thepresent application to denote the geometric area most appropriate forthe sensor element, the term in the present context has considerablybroader meaning than that provided in the prior art. For instance, asapplied to complex, heterogeneous shapes, the “neutral plane” may not,in fact, be a solid plane extending through the object. In the presentcontext, the “neutral plane” can be ovoid, convex, concave, a limitedinternal rectangular shape, or any other shape which is calculated for aparticular solid. It may also be discontinuous, or have voids within anarea otherwise appropriate for the positioning of the sensor element.

Further regarding the term, “neutral plane”, for the purposes of thepresent invention, this area may, in fact, be three-dimensional. Again,through modeling of a complex shape, which can include heterogeneousmaterials, the “neutral plane” could be spherical, conical, pyramidal,and again may be discontinuous or include voids within the areasappropriate for the position of the sensor element.

It is possible to determine a neutral plane for sensor structures of anumber of arbitrary geometry by performing finite element analysis onthe structure subjected to a bending load. Because of the complexity ofthe calculations, this step will be effectively accomplished throughcomputer simulation. The practitioner will then be able to observe thelocation of a plane in which the longitudinal stress is substantiallydiminished, or ideally zero.

In the case of medical devices, there are often secondary stressesproduce in more than a single plane. This can complicate the prior artstress calculation methods considerably, approaching the point wherethese multidimensional forces cannot be accurately accounted for.However, using the teaching of the present invention, thesemultidirectional complicating forces can be resolved into athree-dimensional zone where there is relative quiet for secondarystress forces. The present invention uses currently available computermodeling programs as above to provide for these otherwise impractical tosolve calculations.

With the complete understanding of the mechanical stress dynamics on apressure sensor device provided by the present invention, designapproaches will become apparent to the ordinary skilled practitioner tomaximize the stability of the device. For instance, some portions of thedevice can be built up with bulk materials to shift the neutral plane ina way that enhances the structure for fabrication purposes, or toprovide advantageous alignment with other components in a larger devicewith multiple sensor. In some cases, it may still be useful to attachthe sensor with flexible material to an underlying support structure inorder to maintain the internally consistent neutral plan configurationof the smaller module. In other cases, in may be useful to rigidlyattach the sensor to a larger bulk material to shift the planepreferentially. This optimization will in some cases lead to theidentification of a neutral plane which is off-centered in the sensorbody.

A particularly advantageous inventive design in the case of medicaldevices is a sensing module so carefully attuned by the teaching of thepresent invention that it can accurately provide pressure sensingwithout the necessity of a substantial housing. This innovativeadvancement provides great potential for multiplexing of sensors. Thepotential for such multiplexed devices represents a long felt need inmedical devices, especially in the cardiac arena.

The determination of the “neutral plane” for arbitrary geometries is aconsiderably more complex calculation than the classic examplesdescribed above. However, using the inventive concept, a practitionerwill be able to employ currently available modeling software to identifythe neutral plane. In the examples below, typically micromachinedstructures take the form of a rectangular solid that may haveperforations within its structure. Equally challenging to the classicapproach to neutral plane determination, these devices are typicallyconstructed of diverse material.

Guided by the teachings of the present invention, the neutral plane canbe determined from finite element simulation using finite elementssoftware packages such as ANAYA, Inc. or Cosmos, Structural Research andAnalysis Corporation.

To find the neutral plane using finite element modeling software, oneapproach which can be used by the practitioner is the following:

1) construct a solid model of the pressure sensor chip,

2) apply boundary conditions to constrain certain portions of the chipand apply a load such as a force, pressure or torque to a second portionof the chip,

3) mesh the model,

4) solve the model,

5) examine the resulting plot of strain within the chip to determine theposition that has minimum in-plane stress.

Typically the model is run multiple times while varying a specificdesign parameter with each run. In this way one can determine the effectof the design parameter on the neutral plane position.

The present invention allows for the practical design and constructionof pressure sensors, even at the tight size limitations such as cardiac,ocular and neurological applications. The inventive designs areparticularly applicable in testing environments with heightened pressuredistortion challenges, such as with cardiac and bone sensingapplications.

The present invention allows for the construction of pressure sensingdevices that are from about 0.01 to 10.0 mm in size, such as about 0.1to 5.0 mm in size, and including about 0.3 to 1.5 mm in size.Additionally, the present invention further allows the construction ofpressure sensing devices of considerable thinness, that is from about0.01 to 4 mm in depth, such as about 0.1 to 2.0 mm in depth, andincluding about 0.2 to 1.0 mm in depth.

In representative embodiments, in pressure sensing devices which areconstructed as directed by the present invention, there will be acentral cylindrical area housing the sensing membrane which is eithervoid or contains a material dissimilar from the surrounding supportingmaterial, such as a flexible silicone material. This central area can befrom about 0.1%-10% of the overall volume of the sensor device, such asfrom about 0.5%-5%, and including from about 1%-3%.

FIG. 14A provides a cross-section of a micromachined pressure sensor ofthe prior art showing sensor chip 301, sensor diaphragm 303 and pressuresensitive elements 305 which are provide on sensor diaphragm 303. Thepressure sensor elements 305 in this prior art example will typically bepiezoresistors, as described above. However, the resisters can also beother pressure and/or strain measuring elements or transducers. Oneexample of such alternative strain measuring elements in this contextare vibrating members whose vibrational frequency would change withstrain exerted upon them. FIG. 14B provides a planar view of the priorart pressure sensing device shown in FIG. 14A. Note that the area 307which is the area of the sensor diaphragm which is actively engaged insensing, is fully circular in this view. While the area provided in thisgraphic representation is provided as circular for the purposes ofdemonstration, it will be appreciated that in practice, its area couldbe oval, square, rectangular, or other shapes.

FIG. 15A provides a cross sectional view of the prior art device inFIGS. 14A & B experiencing a bending stress away from sensor diaphragm303. In this case, the sensor chip 301 is now bent. As can be seen inthis view, sensor elements 305 would be stretched when the sensor chip301 experiences flexion stresses in this manner. As shown in the topview, FIG. 15B, the effect is to distort the area 307 from a circular anovoid shape. This force acts on the sensor elements 305 in a mannerwhich serves to distort the elements by elongation.

Conversely, in FIG. 16A an opposite bending stress from that seen inFIGS. 15A & B is applied to sensor chip, that is away from sensordiaphragm 303. As shown in the top view, FIG. 16B, the compressing forceon the surface of the chip causes the area 307 to distort into an ovoidshape, in this case with an axis in the opposite direction from that ofarea 307 shown in FIG. 15B. The result is that sensor elements 305 aresubject to a compression distortion. These views are provided inexaggerated dimensions as compared to actual devices in order to moreclearly demonstrate the effect of the stress, and are diagrammatical innature.

In both the case of a bending stress away from the sensor diaphragm 303shown in FIGS. 15A & B and the bending stress away from the sensordiaphragm 303 shown in FIGS. 16A & B, the sensor output from thepressure sensor 301 would change due to the spanning stress, introducingbackground readings which could distort or fully obscure the pressureinformation which the device is meant to assess. This signal distortionis due to the change in the length of the sensor elements 305 caused bythe bending of sensor chip 301.

FIGS. 17A & B provide a view of one embodiment of the present inventionthat is a sensor device with the sensor element located at or near theneutral plane of the device. FIG. 17A provides a cross section and FIG.17B a plan view of the same device. In this embodiment of the invention,a first sensor chip 309 is provided, with a sensor membrane 311 on itsupward surface. Sensor elements 313 are provided on the sensor membrane311.

In distinction to the prior art examples shown in the prior figures, theinventive embodiment shown in FIGS. 17A & B provides an additional,physical continuation of the sensor chip 309 in the form of a secondsensor chip 315. In this case, and distinct from prior art sensors, thethicknesses of first sensor chip 309 and second sensor chip 315 arechosen so that sensor membrane 311 is in or near the neutral plane ofthe composite chip. A similarly advantageous design can be achieved withdifferent physical dimensions, if there are accommodating materialdifferences in the separate elements of the design. Area 317 is the areaof the sensor diaphragm which is actively engaged in sensing, and isessentially circular in this view.

FIGS. 18A & B show the device provided in FIGS. 17A & B experiencing abending stress in a direction away from sensor diaphragm 311. As isapparent from this view, the bottom surface 319 of sensor chip 309 isexperiencing compression while the top surface 321, of sensor chip 309,is experiencing tension. Yet because the sensor membrane 311 is at theneutral axis, it does not experiencing tension or compression as aresult of these external forces. Therefore, sensor elements 313 do notchange in length. Because, as distinct from the prior art example above,there is no change in length of sensor elements 313, there would also beno change in sensor output due to the straining stress. Note that area317 remains circular, as contrasted with the prior art constructs shownabove.

FIGS. 19A & B are planar and cross section views of the inventive deviceshown in FIGS. 17A & B and with a stress of the opposite magnitudeapplied to the chip from that in FIGS. 18A & B. Note the same principlesapplied to the effect on the sensor elements 313 that is that they donot suffer from distortion. The area 317 again remains circular.

FIGS. 20A & B show cross section and plan views, respectively, of anadditional embodiment of the inventive sensor design. In this case,bottom sensor chip 323 is matched with a top sensor chip 325. Top sensorchip 325 is provided with a cavity 329 which is etched into top sensorchip 325. Bottom sensor chip 323 is provided with a through-hole 327etched through sensor chip 323.

In this case, the pressure sensor measures the difference in thepressure applied to the through-hole 327, the difference betweenpressure in the through-hole 327 and the cavity 329. The cavity 329 canoptionally be filled with ambient air or a gas at ambient pressure. Inthese variants on this embodiment, sensor would be categorized as agauge pressure sensor. Alternatively, the cavity 329 can be filled witha vacuum. In that case, the pressure sensor would be categorized as anabsolute pressure sensor.

FIGS. 21A & B provide a cross sectional and planar view of a thirdembodiment of the present invention. In this case, bottom pressuresensor chip 331 is provided with a bottom through-hole 333. Upperpressure sensor chip 335 is provided with an upper through-hole 337. Inthis embodiment, the inventive pressure sensor responds to thedifference in pressure between the bottom through-hole 333 and the upperthrough-hole 337, which can be connected to different pressure sources.In this configuration, this inventive embodiment would be categorized asa differential pressure sensor.

Amplified Compliant Force Embodiments

In certain embodiments, the subject sensor structures are characterizedby having a transducer element separated from a surface of the compliantmember on which it is associated, i.e., mounted, by a spacer or beamelement, also referred to herein as a lever. Optimizing compliant forcethrough the use of beam elements in the pressure sensor design accordingto these embodiments provides, for the first time, pressure sensordevices of unprecedented small dimensions and robust character whileachieving uniquely fine sensitivity levels.

The sensors of these embodiments provide an unprecedented increase insignal output for pressure sensors for a given amount of pressure. Inthis way, these embodiments provide sensing devices which, whileconstrained in size, are able to provide highly accurate pressurereadings at very small changes in pressure. The force amplificationachieved with devices of these embodiments increases the capacity forsensitivity of micromachined pressure sensors by about 1-1,000 times,such as about 50-500 times, and including about 150-250 times (see FIG.25), as compared to sensitivities achieved with analogous devices inwhich the beam element(s) is not present. When combined with other,standard sensitivity design modifications, these sensitivities can reacheven higher levels.

The present inventive devices and design methods provide the sensordesign engineer a tool by which the apparent strain on the sensormembrane can be magnified or amplified. This tool allows a givenmembrane deflection due to a pressure difference to be dramaticallyamplified. With the inventive approach of employing a beam element, thestrain-measuring elements will experience a larger strain withoutdistortion. As a result, the electrical sensor signal generated by thesensor will be correspondingly increased.

Sensors of these embodiments provide for the detection of smaller andsmaller differences in pressure. The present embodiments allow thedetection of pressures in the range of about 0.01 to 100,000 mmHg, suchas about 0.1 to 10,000 mmHg, and including about 1 to 1000 mmHg.

For a given plate bending, it is possible to calculate the position ofthe where the center of the curvature. It is also possible to calculatethe radius of the curvature of the plate bending. From mechanical textsand from standard engineering analysis, the practitioner will be able tolocate the strain at any given location within the membrane. This strainis typically equal to the distance of that point from the neutral planeof membrane divided by the radius of curvature.

The beam dimensions in the present invention can range from about1-1,000 μm, such as from about 5-500 μm, and including from about 10-100μm.

Additionally, in the present invention, multiple inventive beams can beused on a sensor membrane, for instance from about 1-100 beams, such asfrom about 3-50 beams, and including from about 4-5beams.

The sensors of these embodiments can readily be designed to be able tooptimize the structure to achieve as small an arc as is practicallypossible in order to achieve optimal results. By applying bosses to thesensor membrane and changing the membrane dimensions to reduce to radiusof curvature, one must consider that a larger strain will result

FIG. 22 provides a cross-sectional view of a segment of a membrane orplate undergoing a deflection. This diagrammatical representation is ofa section of pressure-sensing membrane that is experiencing a pressuredifference, causing it to bow. From the discussion above, the formulawhich will be employed by the practitioner in practice of the presentinvention will effect the prior art device of FIG. 22 in the followingmanner. The largest strains will be when z is the largest. However,since the strain element has to be connected to the plate, the greatestpossible z occurs at one or the other surface of the plate.

In FIG. 22 it can be observed from the top surface of the membrane inthe example shown is equal to the thickness divided by 2. On the bottomsurface, z is equal to the negative of the thickness divided by 2. Thisputs a limitation on the maximum strain that the sensor element canexperience for a given radius of bending.

FIG. 23 shows the effect of the inventive design which serves todisplace the strain-measuring elements from the membrane as shown. Thesection 1201 of the pressure-sensing diaphragm is shown in this viewbending about the center of radius 1202. Offset elements, (also referredto herein as spacers or beams) 1203 are provided which serve to displacestrain-measuring element 1204 from the surface of the membrane.

From this depiction, one can observe that z-prime, the distance ofstrain-measuring element 1204 from the neutral axis 1205, is larger thanthe thickness divided by 2. In fact, as practiced in the presentinvention, z-prime can be any arbitrary value. As will be understood bythe practitioner, z-prime may in some cases be limited by some practicalconsiderations such as fabrication techniques.

FIG. 24 provides an example of an alternate embodiment of the presentinvention. This figures shows offset elements 1303 placed on either sideof membrane 1301. In this case, because the offset is below themembrane, the z-prime has a negative value. However, this effect doesnot affect the engineering principle shown in this case.

In a specific embodiment of the present invention, if one were to take apressure-sensing membrane with typical dimensions of a thickness of 1.5μm and in the prior art, the maximum z would be half of that, or 0.75μm. If these standoff elements were manufactured using an additional 1.5μm, the z-prime would now be 1.5+0.75, or 2.25 μm. This engineeringmodification can be accomplished simply and with ease using knownfabrication techniques.

Using the above inventive engineering advances, the inventive devices ofthese embodiments have effectively increased the sensitivity of theprior art pressure sensor design as illustrated in FIG. 22 by 3-fold.This provides a simple exemplification of the present invention.However, using the present inventive techniques, amplification values ofup to 10 or more times can be easily achieved. Thus, the presentinvention increases sensitivity by about 1-100 times, such as about10-80 times, and including about 20-40 times, e.g., as compared to priorart devices, such as those reviewed in FIGS. 1 to 1B.

Practical considerations limit the amplification factor using thissimpler embodiment of the inventive technique to amplifications of about10. However, as shown in FIG. 25, by extending the inventive conceptfurther, in a more advanced, sophisticated embodiment using in-planeamplification, much larger amplification ratios of the strain arepossible. In this case, 100 or several hundred fold increase isavailable using the present inventive approaches.

FIG. 25 a provides a planar view of pressure sensor chip 1501, with apressure sensor membrane 1502. Amplifying structures 1503 and 1504 aredeposited on the pressure sensor chip surface. FIGS. 25B and 25C providecross-sections through this device at different locations marked by theA and A-prime and B and B-prime. As shown in FIGS. 25A, 25B and 25C, theforce-amplifying structures contact the surface of the chip in somelocations but do not contact it in others, that is are freestandingabove the surface in those locations.

An example of an inventive force amplification structure is provided inadditional detail in FIG. 26. Pad 1601 is at a location that is attachedto one part of the pressure sensor membrane and pad 1602 is attached toa second part of the pressure sensor membrane. Using the method of thepresent invention, these locations will be chosen such that there arelocations that experience a large displacement when membrane deflectsdue to an applied pressure.

Using the example of beam 1603, if location 1601 were to move away fromlocation 1602 when a positive pressure was applied, beam 1603 would getpulled toward pad 1601. This movement would cause a rotation of beam1604 whose one end is anchored to pad 1602. However, a mid-point isattached to beam 1603. That rotation would cause a tension on beam 1605which is then attached to a fixed pad 1606. Fixed pad 1606 is attachedto some portion of the chip that would not move. This stationary portionof the chip can be, by example, in the periphery of the membrane.

Beam 1604 is provided with a segment 1607. Comparing the length ofsegment 1607 to the length of the segment 1608, if these lengths areunequal, it will result in either magnification or a reduction in theamplitude of the relative motion of pad 1601 or pad 1602. For instance,if segment 1607 were 10 μm long and segment 608 were 100 μm long, thenthe end of beam 1604 would move 10 times as much as the displacementbetween pad 1601 and pad 1602. This inventive design provides a 10-foldmultiplication in the amplitude of the motion. This improvementtranslates to a 10-fold increase in the strain in beam 1605 and a10-fold increase in the electrical output of the sensor for a givenamount of pressure.

As an example, this particular structure is provided with a mirroredstructure. As such, pad 1606 has its mirror image in pad 1609. Thisinventive design is a convenient approach to fabrication. It also meetsstandards of good mechanical practice by providing symmetry. Thisinventive embodiment has the additional advantage that if, for instance,a strain measuring element 1605, was a piezoresistor, the resistancebetween pad 1606 and pad 1609 can be measured. By observing the changein the resistance, a measure of the strain is provide in those elements,and hence a measure of the pressure.

The above description provides one example of using the inventive leverprinciple to amplify the force. It will be appreciated by the ordinaryskilled artisan that there are many variations on a lever. Equally, howto make levers has been provided in at a previously unavailable level ofsophistication by computer methods for determining the optimum shape oflevers for micromachined structures. In the prior art, such approacheshave been applied to applications like accelerometers and to sort of themicromachined equivalent of a Pantograph. In the latter example, themotivation is to apply a large displacement and cause a very precisemotion. Otherwise, the device is employing a force generator that hasonly a very small displacement which must be amplified.

Additional Features

In some embodiments, the sensor structures further include at least oneconductive wire disposed between two layers of the substrate and coupledwith the at least two transducers, e.g., piezoresistors, fortransmitting sensed data from the sensor structure. For example, theconductive wire may be made of gold, platinum or the like. The layers ofsubstrate may comprise any suitable material or combination ofmaterials, such as a polyamide, a silicone and/or the like. In someembodiments, the at least one wire is operatively coupled with amultiplexed catheter via a conductive liquid or gel. Such multiplexedcatheters are described in co-pending U.S. patent application Ser. Nos.10/764,429; 10/764,127; 10/764,125; and 10/734,490; the disclosures ofwhich are herein incorporated by reference.

The sensor structure may further comprise, at least oneapplication-specific integrated circuit (ASIC) comprising ananalog-to-digital converter for converting analog signals sensed by theresistors into digital signals. Alternatively, the sensor may include atleast one ASIC comprising a voltage-controlled oscillator for convertinganalog signals sensed by the resistors into frequencies. In still otherembodiments, the sensor may further include at least one ASIC comprisinga voltage-controlled duty cycle oscillator for converting analog signalssensed by the resistors into duty cycles. In any of these embodiments,the ASIC may comprise a two-wire circuit, a three-wire circuit or acircuit having more or fewer wires.

One of the largest sources of stress and error on atenth-of-a-millimeter scale pressure sensor is the gradual relaxation ofstress induced by a wire bond. Therefore, some embodiments of thepresent invention eliminate wire bonding from the sensor, for example byusing planar processes to fabricate a flexible lead in an integratedfashion. Thus, the electrical signals are brought to and from the chipvia thin gold wires embedded between two flexible polyamide or siliconelayers of the substrate. In a representative embodiment, these signalsare then conducted to wires embedded in an associated catheter or leadvia a thin layer of conductive liquid or gel. This process stepintroduces a variable resistance in the power, ground and signal lines.

In certain embodiments, a five-wire system as shown in FIG. 27 isemployed to eliminate this variation. FIG. 27 is a representation of asimple integrated electronic device integrated alongside the inventivepressure sensor die. This configuration provides the capacity for thepressure sensor information to be transmitted back to the wire in a morerobust fashion.

On the integrated circuit, shown above the Wheatstone bridge, is acurrent source. This current source can be of many well-known designsproviding a stable amount of current into the resistor bridge. Thisconfiguration produces a voltage relative to ground at the top of theWheatstone bridge, represented by the V_(Bridge). Specifically, theoutput of the top of the Wheatstone bridge goes into an amplifierrelative to ground producing a voltage called V_(Bridge). In someinstances, the output may be that potential. In other cases, it may bescaled by the amplifier, V_(Bridge). V_(Bridge) goes into the analog todigital converter A/D, into the full scale input of that. The analog todigital converter is a ratio-metric converter such that the input signalis ratioed to the full scale signals.

The mid-point to the bridge goes into an amplifier. The output islabeled V_(Pressure). That is then put into the signal version of theanalog to digital converter. In some cases, the V_(Bridge) amplifier andthe V_(Pressure) amplifier are all integrated into the AD converter. Inthese embodiments, four lines go directly into the converter. One of thelines is the ground which represents the bottom of the bridge. Thesecond line is the potential at the top of the Wheatstone bridge thatwould be the full scale. The two inputs would be the signal or theamplified version of the signal. If a differential signal is put in,there are two inputs put in. That would be the ratio metric A to D. Thepurpose of this configuration is to provide a high impedance signal thatcan be sent back to the “can.”

A six-wire system shown in FIG. 28 may be used for a full bridge, in asimilar manner. FIG. 28 provides a modified version of the aboveconfiguration. This configuration provides a system particularlyappropriate for use if the pressure sensor is on a catheter, among otherapplications. In an embodiment where six wires go down the catheter anda Calvin connection is used to drive the current through the Wheatstonebridge, a separate line is used to monitor the potential at the top andbottom of the Wheatstone bridges.

For these six wires, the potentials are then independent of the changesin impedance of those interconnecting wires. If the electronics areintegrated onto the circuit, the above approach can also be used toreduce errors.

All of the above described systems can utilize either an AC or a DCcurrent source. Modification of the electronics to accommodate an ACsystem are possible and are well known in the art for doing samplingwith an AC vs. a DC system. The AC systems remove DC offsets that accrueduring the amplification process.

In one embodiment, the analog pressure signal is converted into either afrequency, or a duty cycle or a digital number before being transmittedover the variable resistance interface. A circuit as shown in FIG. 29may be used in such an embodiment to convert the analog pressure signalinto a single digital number that is then communicated to a computerconnected to the catheter via two or three wire interface. FIG. 29 showsa system that compensates for the stretch of the wafer or the change intemperature of the chip. This compensation is accomplished by having asecond resistor in parallel to the Wheatstone bridge driven by anidentical current source. That goes into an A to D system producing a Sparameter which represents the stress of the wafer changes the gauge andthe gain of the Wheatstone bridge. This S parameter is in addition tothe first version of the system described above which has just thepressure output.

Alternatively, a circuit as in FIG. 30 may be used to provide additionalinformation by measuring the common-mode changes to thepressure-sensitive resistors caused by forces applied to the substrate,such as twisting, bending and/or stretching forces. A temperature sensormay also be added to the sensor to further correct for errors caused bytemperature changes. FIG. 30 shows the resistors all connected to theone supply source and how there are two Wheatstone bridges together. Thebig Wheatstone bridge with the capital R's on the outside is formeasuring the strain or the temperature of the overall system. Thepressure sensor Wheatstone bridge is then used to measure pressure. TheS output is then used to compensate the P output, which is the primarypressure indication.

In certain embodiments, these circuits are all integrated onto the samedie as the pressure sensor. Alternatively, the circuits may beintegrated onto a die which is operatively coupled, e.g., welded, to thepressure sensor die.

Referring now to FIG. 30A, multiple piezoresistors may broadcast dataeither during a predetermined interval or using a dedicated frequency.One embodiment may include, for example, a circuit including avoltage-controlled duty cycle oscillator that converts a differentialpressure signal into an oscillator with a variable duty cycle, as shownin FIG. 30A. The output of such a circuit produces a series of pulses:the ratio of the “on” state to the “off” state is proportional to theabsolute pressure. This series of pulses then becomes the envelope for acarrier frequency of a voltage controlled oscillator. Each of severalsensors may broadcast at a different carrier frequency. An externalmonitor may have a number of electronic filters connected in parallel tothe catheter's output line, with each filter tuned to one of the carrierfrequencies. The output of each filter may, for example, comprise aseries of square pulses whose duty cycle (the ratio of on time to offtime) is proportional to the pressure measured by that sensor. As such,FIG. 30A shows a different type of a circuit that converts pressure intoa more robust signal. Here the pressure sensor resistors are the fourresistors on the left that go up and down with pressure. The two outputsof those four resistors go into analog switches that alternatively go upor down into the same set of sample electronics. Depending on the stateof the sample electronics, each output goes into an integratingcapacitor which is C int. When the potential of C int reaches athreshold, it fires off a logic circuit that resets the integrator andthen starts it over again with the other potential driving it up anddown. The result is a duty cycle oscillator where the ratio of the highvs. low voltage coming out is proportional to the varying pressure. Thisconverts the pressure signal into a variable duty cycle oscillator.

FIGS. 30B & C provide block diagrams of the subject pressure sensorsintegrated with a multiplex system.

A variety of signal conversion techniques may be applied to convert theanalog voltage that represents pressure into a robust signal. Forexample, the analog voltage may be converted into a number using ananalog to digital converter, or the analog voltage may be converted to afrequency using an voltage controlled oscillator, both of which arecommercially available as a component or as a cell layout for anApplication-Specific Integrated Circuit (ASIC). Other less well knowapproaches include a voltage-controlled duty cycle oscillator to convertthe varying pressure signal into a varying duty cycle of a stableoscillator. The circuits of FIGS. 29 and 30 may be incorporated as anASIC and integrated with the sensor using either chip-scale orwafer-scale bonding techniques.

Some embodiments of the sensor device may further include a layer ofmaterial coupled with the substrate such that the layer is positionedbetween the diaphragm and the volume. For example, the layer of materialmay comprise a layer of silicone. In some embodiments, the diaphragm andthe layer of material are separated by a space.

Methods of Fabrication

The sensor structures described herein may be fabricated using anyconvenient protocol. In certain embodiments, the fabrication protocolthat is employed is a microfabrication or micromachining protocol, as isemployed in MEMS fabrication protocols. As is known in the art,Micro-Electro-Mechanical Systems (MEMS) is the integration of mechanicalelements, sensors, actuators, and electronics on a common siliconsubstrate through microfabrication technology. While the electronics arefabricated using integrated circuit (IC) process sequences (e.g., CMOS,Bipolar, or BICMOS processes), the micromechanical components arefabricated using compatible “micromachining” processes that selectivelyetch away parts of the silicon wafer or add new structural layers toform the mechanical and electromechanical devices. Representativefabrication protocols for producing various sensor structures describedabove are now discussed.

FIGS. 31A to U provide a flow diagram display of a representativefabrication method for the inventive pressure sensors. In FIG. 31A,wafer 68 is coated on both its upper and lower surfaces by silicondioxide layers 69 and 70. As shown in FIG. 31B, the next fabricationsteps provide the deposit of sacrificial layer 71 on silicon dioxidelayer 69. Sacrificial layer 71 is typically composed of copper oraluminum. In other embodiments, sacrificial layer 71 can be selectedfrom a variety of other materials well known to the ordinary skilledartisan.

Sacrificial layer 71 is optionally coated with etched-up layer 72.Etched-up layer 72 may be composed of a typical etched up layeringmaterial such as chromium or titanium. In representative embodiments,etched-up layer 72 is composed of titanium tungsten.

The resulting structure is then coated with second sacrificial layer 73.Second sacrificial layer 73 may be composed of the same or a differentmaterial as the etched-up layer 72. Second sacrificial layer 73 is thencoated with second etched-up layer 74. The combination of those layers,that is the sandwich structure formed of second sacrificial layer 73 andsecond etched-up layer 74, is patterned into two mesas 75 using standardlithographic techniques, such as lithography or wet etching.

As shown in FIG. 31C, the first sacrificial layer 71 and etched-up layer72 are patterned photolithographically. As shown in FIG. 31D, thesurface structures on the developing pressure sensor, including thevarious sacrificial layers and other structures, are coated withstructural layer 76. Structural layer 76 may be composed of silicondioxide, silicon nitrite, or silicon oxynitride. The material to producestructural layer 76 is typically deposited by plasma enhanced chemicalvapor deposition. Alternatively, there are a number of similar standardsemiconductor techniques for depositing the material of structural layer76 which can be employed.

As shown in FIG. 31E, structural layer 76 is a planarized layer. Thisplanarization is preferably accomplished with chemical mechanicalpolishing. The planarization of structural layer 76 exposes etched upperlayer 77 at the surface of mesas 75.

As shown in FIG. 31F, piezoresistor layer 78 is deposited and patternedon the top surface of structural layer 76. In certain embodiments,piezoresistor layer 78 is platinum or polycrystalline silicon. In thecase of the choice of platinum for the piezoresistor layer 78, thematerial is patterned with a lift off technique. In case of the choiceof polycrystalline silicon platinum for the piezoresistor layer 78, thematerial is deposited and then patterned photolithographically witheither dry etch or wet etch.

As shown in FIG. 31G, the piezoresistor layer 78 is coated with a secondstructural layer 79. Second structural layer 79 can be selected from oneof a number of different materials, such as silicon nitride, siliconoxide, or silicon oxynitride. Proceeding to FIG. 31H, secondpiezoresistor layer 80, such as platinum, is deposited and patterned onthe surface of second structural layer 79. In FIG. 31I, third structurallayer 81 is deposited and patterned on the surfaces of second structurallayer 79 and second piezoresistor layer 80. Third structural layer 81may be selected from silicon nitride, silicon dioxide or siliconoxynitride, although it can be composed of other appropriate materials.

As shown in FIG. 31J, a top silicon dioxide layer 82 is deposited overthe entire exposed surface areas of second structural layer 79, secondpiezoresistor layer 80, and third structural layer 81. As shown in FIG.31K, hole 83 is then made through top silicon dioxide layer 84 and thetwo underlying silicon dioxide or silicon nitride structural layers 85and 86 to expose sacrificial layer 87.

As shown in FIG. 31L, sacrificial material is removed leaving cavity 88.The sacrificial material can be removed by any suitable means, such asusing a wet chemical etching such as sulfuric acid, nitric acid or anelectrochemical etch. As shown in FIG. 31M, hole 89 is sealed with plug90. Plug 90 is preferably a metal, such as gold. The metal to produceplug 90 is deposited and then etched. This approach results in the metalmaterial remaining only in the plug portion of the wafer.

As shown in FIG. 31N, simultaneously with the fabrication of plug 90,gold or other suitable metal is patterned into bond pads 91. As shown inFIG. 310, bottom layer 92 of flexible material, such as polyimide, isdeposited and lithography patterned. FIG. 31P shows the exposed surfaceof bond pads 91, bottom layer 92, and well as part of plug 90 coatedwith layer of gold 93. Layer of gold 93 is deposited andphotolithographically patterned to create traces from the sensor area ofthe die to the bond pad 91.

As shown in FIG. 31Q, the resultant structure is coated with additionallayer 94, such as polyimide. As shown in FIG. 31R, etched mask 95 isdeposited and photolithographically patterned. Typically, the materialfor etched mask 95 is aluminum, less preferably photo resist.

As shown in FIG. 31S, the same or different etched-up material 96 isdeposited on the front side of the wafer. FIG. 31T shows opening 98 madein the back side of the wafer. FIG. 31U shows the result of the nextfabrication step, where the various etched-up materials, as well asaluminum and photo resist, are stripped from both side of the wafer. Inthis manner, the structure is revealed, yielding the final inventivepressure sensing device.

A simplified process for manufacturing the inventive low-drift pressuresensors is shown starting in FIG. 32A. The initial fabrication beginswith silicon on insulator wafer 211, which is composed of silicon layer213, a silicon dioxide layer 215, and a second silicon layer 217.Silicon on oxide wafers are commercially available, or, alternatively,can be manufactured by number of techniques well know to the skilledartisan. Fabrication of this component is typically accomplished bybonding two silicon wafers together with silicon fusion bonding,followed by grinding and polishing back one of the wafers to get thedesired thickness of silicon layer 217. This starting wafer can then becoated with silicon dioxide layer 219. This fabrication step is flowedby spin coating with photo resist the chip is then exposed and patternedusing standard lithographic techniques into the opposite of the desiredresistor pattern, shown in features 221.

As shown in FIG. 32B, the wafer is then coated with the piezoresistormaterial 223, typically platinum, where the platinum covers both thesilicon dioxide 225 and also the photo resist 227. The platinum can bedeposited by sputtering, evaporation, or electroplating, or by a numberof standard semi-conductor deposition techniques.

As shown in FIG. 32C, following platinum deposition, the unwantedplatinum is removed by immersing the wafer in a solvent that dissolvesthe photo resist. In this manner, any platinum is lifted off that iscoating the photo resist, leaving the remaining platinum 229 in thedesired areas in the shape of the resistor pattern.

As shown in FIG. 32D, the next step in this particular fabricationprocess is that the boss layer is deposited. The boss layer can besilicon nitride, silicon dioxide, or amorphous silicon or polycrystalline silicon among other material choices. The boss layer istypically deposited by plasma enhanced chemical vapor deposition, thatis PECVD. Other alternative deposition processes are sputtering,evaporation, or a number of standard semiconductor depositiontechniques. The layer would be patterned as provided in FIG. 32E.Referring to FIG. 32D, nitride layer 231 is provided.

In FIG. 32E, the nitride layer 233 is patterned to define boss 235 andthe edges of the membrane 235. This construct may be patterned withphoto lithography, followed by either chemical etching or plasma etchingusing standard semiconductor fabrication techniques. Preferably theconstruct is patterned with plasma etching, typically in a sulfurhexa-fluoride plasma. Optionally at this stage an additional platinumlayer can be deposited on top of the boss layer 235 and then patternedwith photolithography as shown above, but for simplicity is omitted fromthis figure.

As shown in FIG. 32F, a hole is patterned in the backside of the waferwhere photo resist 237 would be applied to the backside of wafer 239. Anopening 241 is etched through the wafer, preferably with plasma etching,and most preferably with deep reactive ion etching.

As shown in FIG. 32G, buried silicon dioxide 243 is removed in from thearea of the membrane 245 that is exposed in the opening 247. The silicondioxide 243 is removed with wet chemical etching, such as immersion inhydrofluoric acid or with plasma etching, completing the fabrication.

FIG. 33 provides a simplified schematic showing of one embodiment of aninventive manufacturing method which allows the production sensorstructures in which the sensor element is positioned at least proximalto the neutral plane of the structure. In FIG. 33, Silicon wafer 341 isprovided with membrane material 343 on one surface. Alternatively,membrane material 343 can consist of a silicone on insulator layer or ahighly doped silicon layer. A typical fabrication step would be todeposit a sensor element layer 345 on top of the membrane material. Inone embodiment, the sensor element layer 345 is a metal piezoresistorsuch as platinum. In alternative embodiment, sensor element layer 345 isa diffused silicon piezoresistor that would then be patterned intosensor elements 347. Simultaneously a second chip, wafer 349, would havecavity 351 photolithographically defined and etched. The two resultingwafers would then be joined together in intermediate structure 353. Anaccess port 355 to the membrane would be etched into intermediatestructure 353.

FIGS. 34A to H provide a flow diagram of a simplified fabricationsequence for making one on the present inventive devices. FIG. 34A showsa starting substrate with a wafer 1401, and membrane layer 1403. Theetch-stop layer 1402 is optional. In a typical device, wafer 1401 thenwill be a silicon. Etched-up layer 1402 would typically be silicondioxide, and membrane layer 1403 would also typically be silicon.

In FIG. 34B, offset layer 1404 is deposited on top of wafer 1401. InFIG. 34C offset layer 1404 is patterned to make openings or features1405 in offset layer 1404. In FIG. 34D a strain-sensing material 1406 isdeposited on top of the offset layer 1404. Strain-sensing material 1406can be a piezoresistive metal such as platinum. Alternatively,strain-sensing material 1406 can be a diffused resister into a siliconlayer. In FIG. 34E, a hole is etched through the back of chip 1407 todefine the sensing membrane. FIGS. 34F, 34G and 34H provide planar viewsof the constructs illustrated in FIGS. 34A, 34B and 34C, respectively.

FIGS. 35A to 35F provide a flow diagram depiction of one embodiment ofthe present inventive fabrication method to make the inventive in-planelever structure. In FIG. 35A, the fabrication begins with wafer 701.Wafer 701 may conveniently be a silicon wafer. Deposited on wafer 701 isetch-stop 702. Etch-stop 702 can be silicon dioxide. Etch-stop 702 issurfaced with membrane layer 703. Topping these layers is sacrificiallayer 704. In FIG. 35B, sacrificial layer 704 is patterned to form aseries of features 705.

The features 705 in the sacrificial layer 704 represent areas wheremechanical structure of the inventive device will not touch theunderlying membrane. The holes 706 in the sacrificial layer 704 arepositioned in places where the lever layer 707 will be attached to themembrane. In FIG. 35C, lever layer 707 is deposited. Lever layer 707 maybe constructed of polycrystalline silicon.

In FIG. 35D the intermediate chip is patterned into structures 708.Structures 708 represent the various lever arms and anchor padsdescribed in the previous figure. In FIG. 35E, the sacrificial layer 704is etched away. If, by example, silicon dioxide is used as thesacrificial layer 704, it can be etched away with hydrofluoric acid. Inwhatever manner sacrificial layer 704 is etched, freestanding leverstructures 708 are produced.

FIG. 35F describes the last step in this embodiment of the presentinventive fabrication method. In the backside of the chip hole 709 isetched to define the membrane area.

Systems

Also provided are systems that include the subject sensors. The systemsinclude the subject sensor structures, as well as additional componentsthat find use in particular pressure sensing applications. For example,in certain embodiments, the sensor system may include a processor forconverting responses of the transducers of a sensor structure tomeasurements of pressure changes in the volume being monitored. In someembodiments, the system may include a multiplexed catheter coupled withthe at least one conductive wire via a conductive liquid or gel. Atleast one additional pressure sensor may also be located apart from thesensor structure for providing measurement of a gauge pressure.

A particularly advantageous design for semi-permanent and permanentembodiments, i.e., implantable embodiments, of the inventive low-driftpressure sensor is the approach of using one common connection and asingle wire running to each individual connection. This is a bus typeconfiguration. In this design of the innovative low-drift pressuresensing, the opportunity is provided for a long string of pressuresensors implanted along the length of an implanted device, such as acardiac catheter.

In contrast to the temporary configurations, a bus configurationprovides a single wire or conductor which serves all of the low-driftsensor components for one side of the electrical connection. This busconfiguration allows a small denier size, which can be pivotal inproviding for instance, a cardiac timing device in an acceptable formfor semi permanent or permanent uses. This bus configuration also playson the strength of the small dimensions available for the low-driftpressure sensor components. This configuration is further described inPublished PCT Application No. WO 2004/052182 and U.S. patent applicationSer. No. 10/734,490, the disclosure of which is herein incorporated byreference.

In the permanent implant embodiment of the present inventive low-driftpressure sensing device system, conductors are selected which have arelatively high fatigue life. The capacity to survive 400 million cyclesprior to failure is the typical requirement for long term implantcardiac devices. For the construction of devices meeting theserequirements, several design approaches are particularly suitable.

For permanent implant cardiac timing devices, the inventive low-driftpressure sensors may be incorporated into the satellite technology whichhas been developed by some of the present inventors. These applicationsprovide multiplexing systems developed by some of the present inventorswith which the present inventive low-drift pressure sensors veryusefully employed.

In this prior work by some of the present inventors is described the useof pressure sensors to ascertain dynamic cardiac parameters for cardiacresynchronization. This system is described in part in currently pendingpatent applications U.S. patent application Ser. No. 10/764,429 entitled“Method and Apparatus for Enhancing Cardiac Pacing”, U.S. patentapplication Ser. No. 10/764,127 entitled “Methods and Systems forMeasuring Cardiac Parameters”, U.S. patent application Ser. No.10/764,125 entitled “Method and System for Remote HemodynamicMonitoring” all filed Jan. 23, 2004, and U.S. patent application Ser.No. 10/734,490 entitled “Method and System for Monitoring and TreatingHemodynamic Parameters” filed Dec. 11, 2003. These applications areherein incorporated into the present application by reference in theirentirety.

Some of the present inventors have developed Doppler, strain gauge,accelerometer, and other wall motion and other cardiac parameter sensingwhich can be employed synergistically with the present inventioneffectively in the comprehensive systems described above. Some of theseare embodied in currently filed provisionals; One Wire MedicalMonitoring and Treating Devices, U.S. Patent Application No. 60/607280filed Sep. 2, 2004, and Implantable Doppler Tomography System U.S.Patent Application No. 60/617618 filed Oct. 8, 2004. These applicationsare incorporated in their entirety by reference herein.

In addition, the subject systems may include a processing element whichis configured to run the system to provide the desired application, suchas the various representative applications discussed below.

Methods

Also provided are methods of using the subject sensors structures andsystems that include the same. In general, methods of detecting, i.e.,sensing, pressure changes in a volume are provided. In practicing thesubject methods, a sensor structure of the present invention iscontacted with a volume to be monitored. Contact of the sensor and thevolume is achieved using any convenient approach, where the particularapproach will vary depending on the location of the volume. In certainembodiments where the volume is an internal location of a patient, suchas a heart chamber, contact is achieved by implanting the sensor at asuitable location in contact with the volume.

Contact of the sensor and the volume is then maintained over the periodof time that pressure changes are to be detected or monitored. While thesensor is contacted with the volume, a suitable voltage is applied tothe input(s) of the strain transducer elements. The resultant output isthen monitored, and the resultant output signal is used to detectchanges in pressure of the volume, as is known in the art. Because thesubject sensors are low drift sensors, an implanted sensor can beemployed to accurately monitor pressure changes in a volume for extendedperiods of time without recalibration following implantation, e.g., forperiods of at least about 1 day, such as at least about 1 week,including at least about 1 month or longer, such as at least about 6months, at least about 1 year, at least about 5 years, etc.

The subject methods and devices find use in any of a number of differentcontexts. In one embodiment, for example, a sensor device may beimplanted in a body chamber to measure and monitor pressure therein. Forexample, a sensor (or sensors) may be implanted in one or more heartwalls to monitor pressure changes in one or more heart chambers.Deflections in a diaphragm of a sensor device may be converted topressure measurements which may be used, for example, by a physician tohelp guide treatment decisions. Such data may also be used toautomatically adjust a pressure-responsive pacemaker implanted in apatient. Applications in which the subject devices and methods find useare further described in: U.S. patent application Ser. No. 10/764,429entitled “Method and Apparatus for Enhancing Cardiac Pacing”; U.S.patent application Ser. No. 10/764,127 entitled “Methods and Systems forMeasuring Cardiac Parameters”; U.S. patent application Ser. No.10/764,125 entitled “Method and System for Remote HemodynamicMonitoring”; and U.S. patent application Ser. No. 10/734,490 entitled“Method and System for Monitoring and Treating Hemodynamic Parameters”;the disclosures of which are herein incorporated by reference.

As indicated above, the present invention provides methods, apparatusesand systems for employing low drift, permanent implanted pressuresensors for optimizing medical treatment, such as for cardiacresynchronization intervention, arrhythmia management, ischemiadetection, coronary artery disease management, and heart failuremanagement, among other types of applications. These representativeapplications are now reviewed in greater detail below.

There are special clinical advantages for the inventive permanentinternal pressure sensors capacity to provide remote, real time internalpressure data. For instance, by means of the inventive devices, pressuresensor data can be provided directly to the physician's office formonitoring patient progress, allowing the physician to effectivelymodify pharmaceutical intervention without requiring patient travel.This application of the present invention is particularly advantageousfor patients in remote areas.

Additionally, using the present inventive implantable pressure sensordevices, physicians are able to monitor patients during normal dailyactivities. This capacity of the inventive implantable pressure sensorsencourages heart failure patients to resume health promoting increasesin physical exertion. In some cases, patients will, for the first time,be able to undertake a program of increasingly active exercise thatincreases the quality of their lives and provides overall clinicalimprovement.

The inventive implantable pressure sensors can be effectively employedby specialists, such as congestive heart failure cardiologists, toaddress a patient's medication, diet and exercise regimen in response toreal time physiologic data such as cardiac output which may bedetermined from implantable pressure sensor readings.

The totally implantable system embodiment of the present invention,which may include intracardiac leads and other structures utilizingpressure sensors, can be further modified in another embodiment of thepresent invention to optimize clinical improvements.

A representative application for the inventive permanently implantablepressure sensors within the human body, with particular focus on thehemo-dynamics system, is implantation in one or more of the fourchambers of the heart. In such locations pressure sensors give a globalindicator of myocardial performance. Such a global indicator essentiallyintegrates all the various flows as well as contractility contributionsof separate myocardial wall segments. These indicators further provideperformance indicators of the various heart valves in combination. Thisglobal assessment is a very valuable tool in assessing and treatingheart failure.

Ratio-metric analysis of data from the present implantable pressuresensor devices can be used to derive clinically important parameters,such as ischemic burden of a patient's heart, cardiac output, and othervaluable physiologic information. Ratio-metric analysis is thecomparison of a pressure signal in one or more chambers with other suchsignals, or indeed other more local signals. Ratio-metric analysis hasbeen described previously in the context cardiac wall motion, localstrain and other factors. This analysis as applied to the presentinvention will be well understood by the skilled artisan.

Other applications for pressure sensors permanently implanted within thehuman cardio vascular system include providing measurements of coronaryartery disease progression. This application is accomplished byimplanting a plurality of sensors along the distribution of, forexample, a coronary artery. The appropriate placement of the inventivesensor can also be accomplished by incorporating the inventive micropressure sensors within the proximal and distal end of a coronary stent.The pressure gradient which is provided by the inventive device is usedto potentially derive flow data and also the resistive resistance toflow between the two pressure sensors. The change in this resistanceover time can be used as an indicator of, for example, re-stenosis orprogression of coronary artery disease that is arteriosclerosis.

Artificial heart valve analysis using the inventive implantable pressuresensors is related to coronary artery disease assessment. Artificialheart valve analysis can be accomplished with pressure sensor placementwithin the chambers of the heart proximal and distal. This placementwould be on the inter-cardiac area, or within each chamber heartseparated by either a natural or an artificial heart valve. In thelatter case, the sensors are incorporated into the artificial heartvalve itself. In the former case, the sensors could be implanted throughless invasive means, or at the time of a reparative surgery, such asangioplasty. The inventive implantable pressure sensors so positionedprovide a real time indication of the pressure gradient across a valve.This data can be used to determine the degree of leakiness or stenosisof said valve. Such sensors also provide information on how leakiness orstenosis of the valve is progressing over time.

When combined with other sensors, additional information can be derivedfrom the present implantable pressure sensors. The additional sensors,such as those previously described, would be located within chambersassessing the degree to which pressure is being generated. By example,the chambers selected can be the left ventricle. As compared to theinter-cavity pressures in the left ventricle, that gradient across themitral valve and the wall strain across one or more segments of theheart provides a very comprehensive picture of how a heart isperforming. The left ventricular performance and the variouscontributions of contractility, synchrony vs. dissynchrony and mitralregurgitation, for example, can be quantitatively assessed.

A drawback in today's management methods is that a multiparametricanalysis is often problematic. Clinically, in many cases decisionsregarding valvular replacement, that is surgical valvular replacement,are made by the clinician on a less objective basis than would bedesirable. The present invention thus makes clinically availablemultiparametric analysis information, providing for better informed casedecisions.

Another application for the inventive permanently implantable pressuresensor is in an essentially fully implantable Swan Ganz, or pulmonaryartery catheter. In this implementation the well understood pulmonaryartery catheter would be employed. A pulmonary artery catheter istypically introduced from a jugular or subclavian venous orientationpassing through the right atrium, right ventricle, right ventricularoutflow track and into the pulmonary circulation. Such catheters whencontaining the inventive implantable pressure sensors provide theclinician with both right atrial and right ventricular pressures.

Pulmonary artery pressure can also be assessed using the inventiveimplantable pressure sensors. This can be accomplished when the catheteris wedged by blowing up and inflating a balloon. That approach providesa pressure through an essentially a static column of fluid to the leftatrium. A pulmonary capillary wedge pressure typically correlates verywell to the left atrial pressure. The reading is obtained from the rightside of the heart. Furthermore, by injecting heat indicator dye or coldfluid and integrating a signal in a appropriate sensor, the distal tipof the pulmonary catheter, e.g., Swan Ganz catheter, the clinician isable to determine cardiac output on a reasonably reliable basis.

With the inventive micro pressure sensors a permanently implantable ortemporarily implantable pulmonary artery catheter can be assembled. Withthis device, the pressure sensors may be left in the pulmonary artery ina stent like structure. Alternatively, the pressure sensors are deployedalong a catheter structure passing through the heart but terminating ina subcutaneous coil. This configuration provides for the data to becommunicated to the outside world.

The inventive devices being capable of transmitting information toremote sites when implanted in the patient enables congestive heartfailure patients a new level of freedom and safety. For example, withsuch a device, a patient is able to move to a regular bed and out of ICUwhen medications are being titrated. Previously, invasive approacheswere required to provided the extremely detailed hemo-dynamic monitoringof cardiac performance needed for such titrations.

Currently in such a situation, the temporary implantable Swan Ganzcatheter is typically removed after several days, at which point thepatient moves home. However, by fully implanting the inventive systeminto a permanently implantable form, the patient is no longer tetheredto the various equipment that needs to be in the intensive care unit.

Furthermore, the permanently implanted device eliminates a direct routefor infectious agents to enter the central circulation of the patient.This reduces the not insignificant risk of sepsis and other infections,which is significant in these patients who typically have impairedcardiac function and reduced cardiac output. For these and otherreasons, such patients are more vulnerable to infection.

Another application for the subject invention is using pressure sensorsdeployed within a triple A stent graft. This is the case where anabdominal aortic aneurism is repaired by an endovascular graft.Typically, the endovascular graft is introduced from the femoralapproach in a minimally invasive manner. The present implantablepressures sensors are advantageous for detecting any issues with graftsealing. The necessary information can be obtained by pressure sensorson the outside of the stent graft in the area of the aneurism in orderto provide early detection of leaks.

An advantage of the inventive implantable pressure sensors in this caseis that they eliminate or reduce the need for routine follow up CTscans. Such scans are currently required to follow progression of theaneurism after implantation of the endovascular stent graft. Clinically,typically issues in such cases are migration of the stent graft overtime and loss of sealing.

Another new application provided by the inventive implantable pressuresensors uses a similar approach to the stent graft described above. Inthis case, a micro stent graft is provided within a neurovascularaneurism. Such aneurysms are, for instance, one closed off through amircoinvasive or minimally invasive approach via catheters, such as aGuglielmi Detachable Coil (GDC). This arrangement allows the clinicianto continue monitoring the pressure profile of that procedure, or forthe period following the procedure.

In another application, the inventive permanent pressure sensors areimplanted in a peripheral artery or a central artery for purposes ofdetermining the pulse pressure. The pulse pressure is used to correlatethe appropriate calibration to the cardiac output of the patient. Thisembodiment of the inventive device can be used to improveresynchronization of a dissynchronous heart in the case of cardiac resynchronization therapy or management of congestive heart failurepatients by pharmacologic means.

Cardiac resynchronization therapy is an important new medicalintervention for patients suffering from congestive heart failure. Incongestive heart failure, symptoms develop due to the inability of theheart to function sufficiently well as a mechanical pump to supply thebody's physiologic needs. Congestive heart failure is characterized bygradual decline in cardiac function punctuated by severe exacerbationsleading eventually to death. It is estimated that over five millionpatients in the United States suffer from this malady.

The aim of resynchronization pacing is to induce the interventricularseptum and the left ventricular free wall to contract at approximatelythe same time. Resynchronization therapy seeks to provide a contractiontime sequence which will most effectively produce maximal cardiac outputwith minimal total energy expenditure by the heart. Prior to the presentinvention, there were no useful clinically available means ofdetermining optimal CRT settings on a substantially automatic or areal-time, machine readable basis.

The optimal timing is calculated by reference to hemodynamic parameterssuch as dP dt, the first derivative of the pressure waveform in the leftventricle. The dP dt parameter is a well-documented proxy for leftventricular contractility. In this manner, synchrony is assessed betweenvarious parameters such as a dP dt, the first derivative of the pressurecurve correlated to maximal relative velocity during systole towards thecenter of the ventricle. Also provided is the actual maximum position ofdisplacement on a net basis of the monitored wall segments towards thecenter. The present inventive implantable pressure sensors allow realtime analysis of the efficacy of a particular resynchronizationelectrode placement or pacing timing, as well as providing immediate,real time hemodynamic parameters.

The clinically established data point for CRT therapy ispressure-pressure loops. In the general case it is thought that in thehealthy heart, both ventricles contract at the same time. In that case,peak pressures are achieved in both ventricles simultaneously. This testhas been employed as a measure of potential synchrony.

In dissynchronous hearts, the pressure peak typically occurs atdifferent times, suggesting that the muscle is contracting at differenttimes. This difference in contraction can now be directly measured withthe present inventive implantable pressure sensor devices. Comparison toRV and/or LV pressures will add global data to other current methods forassessing heart contraction synchrony.

Additional clinical cardiology uses for the inventive implantablepressure sensors include applications as ischemia detectors. It is wellunderstood that, before biochemical or electrical markers of cardiacischemia present themselves, wall motion is first affected with theischemic region showing increased stiffness and decreased contraction,resulting in changed pressure profiles, whether absolute or relativebetween heart chambers. Such changes as they effect internal cardiacpressures can be readily detected by the implantable pressure sensorsystem currently invented.

The present invention can establish a baseline pressure reading forpatients at risk for ischemia. This reading provides a profile ofnormal/beginning heart pressure in a particular patient. The clinicianthen sets a pressure standard, variation beyond which an alert would beprovided.

The inventive implantable pressure sensors can be employed as arrhythmiadetectors. Currently implantable defibrillator systems are challenged bydifferentiating between a variety of benign and malignant arrhythmiasrelying as they do primarily on electrical means of discrimination. Realtime dynamic sensing of changed internal cardiac pressures using thepresent inventive implantable pressure sensors marks a significantadvantage in detecting arrhythmias.

Using the implantable pressure sensor devices of the present invention,the timing and displacement of the contraction from any heart chambercan be assessed. In this way, the maximum contraction can be stimulatedto occur at the time most efficient from the standpoint of producing thegreatest hemodynamic output for the least amount of effort.

Other derived hemodynamic parameters will be recognized by the artisan.In an additional embodiment of the present invention, additional sensorsdeployed along other areas of the heart provide data that providecomplete characterization of the function of the ventricle orventricles. This wealth of real time information is continuouslyavailable to the clinician on a permanent implantable basis. Thisongoing pressure sensor data can also be provided to the pacing systemcontroller directly. This allows automated optimization of pacing timingto that which will prove most clinically beneficial.

Kits

As summarized above, also provided are kits and systems for use inpracticing the subject methods. The kits and systems at least includethe subject sensors and/or systems that include the same, as describedabove. The kits and systems may also include a number of optionalcomponents that find use with the subject sensors, including but notlimited to, implantation devices, data analysis elements, processingalgorithms recorded on suitable media, etc.

In certain embodiments of the subject kits, the kits will furtherinclude instructions for using the subject devices or elements forobtaining the same (e.g., a website URL directing the user to a webpagewhich provides the instructions), where these instructions are typicallyprinted on a substrate, which substrate may be one or more of: a packageinsert, the packaging, reagent containers and the like. In the subjectkits, the one or more components are present in the same or differentcontainers, as may be convenient or desirable.

It is evident from the above discussion and results that the subjectinvention provides for improved pressure sensor devices that areparticularly suited for use in implant applications. Advantages of thesubject sensors include low drift and/or high sensitivity. As such, thesubject invention represents a significant contribution to the art.

While the present invention has been described with reference to thespecific embodiments thereof, it should be understood by those skilledin the art that various changes may be made and equivalents may besubstituted without departing from the true spirit and scope of theinvention. In addition, many modifications may be made to adapt aparticular situation, material, composition of matter, process, processstep or steps, to the objective, spirit and scope of the presentinvention. All such modifications are intended to be within the scope ofthe claims appended hereto.

1. An implantable pressure sensor structure comprising: a substrate; acompliant member mounted on said substrate in a manner such that saidcompliant member has first and second opposing exposed surfaces; and atleast one strain transducer associated with a surface of said compliantmember; wherein said pressure sensor structure is a low-drift pressuresensor structure.
 2. The structure according to claim 1, wherein saidstructure further comprises an integrated circuit.
 3. The structureaccording to claim 1, wherein said substrate comprises an opening andsaid compliant member spans said opening.
 4. The structure according toclaim 3, wherein said structure comprises at least first and secondstrain transducers mounted on a surface of said compliant member.
 5. Thestructure according to claim 1, wherein said structure exhibits a driftof no more than about 1 mmHg/year.
 6. The structure according to claim1, wherein said structure exhibits little or no drift over a period offrom about 1 to about 40 years.
 7. The structure according to claim 1,wherein said structure has a length along an edge of no more than about500 μm and width of nor more than about 100 μm.
 8. The structureaccording to claim 1, wherein said structure has a sensitivitysufficient to measure pressure changes in a volume of about ±1 mmHg. 9.The structure according to claim 3, wherein said first and second straintransducers are piezoresistors.
 10. The structure according to claim 9,wherein said piezoresistors are fabricated from a stable gauge material.11. The structure according to claim 10, wherein said stable materialcomprises platinum.
 12. The structure according to claim 11, whereinsaid stable gauge material is pure platinum.
 13. The structure accordingto claim 11, wherein said stable gauge material is a platinum alloy. 14.The structure according to claim 10, wherein said piezoresistors arecovered by a passivating layer.
 15. The structure according to claim 14,wherein said passivating layer has a thickness ranging from about 50 nmto about 100 nm.
 16. The structure according to claim 14, wherein saidpassivating layer comprises silicon nitride.
 17. The structure accordingto claim 9, wherein said compliant member comprises single crystalsilicon.
 18. The structure according to claim 4, wherein said first andsecond strain transducers are positioned on the same surface or opposingsurfaces of said compliant member so that their outputs respondoppositely to deflection of said compliant member resulting fromdifferential pressure across said compliant member but respond similarlyto deformation of said substrate.
 19. The structure according to claim18, wherein said first and second strain transducers are positioned onthe same surface of said compliant member.
 20. The structure accordingto claim 19, wherein said first and second strain transducers arepositioned symmetrically on said same surface on opposite sides of aline of symmetry.
 21. The structure according to claim 20, wherein saidfirst and second strain transducers are positioned adjacent to eachother on a surface of said compliant member on one side of a line ofsymmetry.
 22. The structure according to claim 18, wherein said firstand second strain transducers are positioned on opposing surfaces ofsaid compliant member.
 23. The structure according to claim 22, whereinsaid structure further comprises third and fourth strain transducers onopposing surfaces of said compliant member.
 24. The structure accordingto claim 23, wherein said strain transducers are piezoresistors.
 25. Thestructure according to claim 22, wherein said first and second straintransducers are directly opposed to each other.
 26. The structureaccording to claim 18, wherein said structure further comprises a bossmember on at least one surface of said compliant member.
 27. Thestructure according to claim 18, wherein said structure furthercomprises first and second boss members on opposing surfaces of saidcompliant member.
 28. The structure according to claim 23, wherein saidstructure further comprises third and fourth strain transducers onopposing surfaces of said compliant member.
 29. The structure accordingto claim 28, wherein said structure further comprises first and secondboss members on opposing surfaces of said compliant member.
 30. Thestructure according to claim 1, wherein said compliant member ispositioned at least proximal to said structure's neutral plane.
 31. Thestructure according to claim 30, wherein said structure comprises anupper rim member positioned on a top surface of said compliant member.32. The structure according to claim 30, wherein said second exposedsurface bounds an enclosed volume in said substrate.
 33. The structureaccording to claim 30, wherein said second exposed surface bounds anopen volume in said substrate.
 34. The structure according to claim 1,wherein said at least one strain transducer is separated from saidsurface of said compliant member by a spacer.
 35. The structureaccording to claim 34, wherein said spacer separates said sensor fromsaid compliant member by a distance ranging from about from about 1 toabout 1,000 μm.
 36. The structure according to claim 34, wherein saidstructure comprises two or more transducers each separated from saidsurface by a spacer.
 37. A system comprising: a conductive member; and aphysiological pressure sensor operatively coupled to said conductivemember, wherein said physiological pressure sensor comprises: asubstrate; a compliant member mounted on said substrate in a manner suchthat said compliant member has first and second opposing exposedsurfaces; and at least one strain transducer mounted on a surface ofsaid compliant member; wherein said pressure sensor structure is alow-drift pressure sensor structure.
 38. The system according to claim37, wherein said system comprises a plurality of said physiologicalpressure sensors operatively coupled to said conductive member.
 39. Thesystem according to claim 37, wherein said system further comprises anenergy source coupled to said conductive member.
 40. The systemaccording to claim 37, wherein said system further comprises aprocessing element for determining pressure changes in a volume inresponse to output signals from said transducer.
 41. The systemaccording to claim 37, wherein said system is configured to be implantedinto a patient.
 42. The system according to claim 41, wherein saidsystem is configured so that said sensor is positioned on a heart wallupon implantation into a patient.
 43. A method for fabricating apressure-sensor structure, said method comprising: positioning a layerof a compliant material on a surface of a first substrate; producing atleast one strain transducer on a first surface of said compliantmaterial opposite said substrate to produce a pressure-sensor structure;wherein said pressure sensor structure is a low-drift pressure sensor.44. The method according to claim 43, wherein said method is amicrofabrication method.
 45. The method according to claim 44, whereinsaid method comprises a photolithographic method.
 46. The methodaccording to claim 43, wherein said method further comprises producing aboss member on said first surface of said compliant layer.
 47. Themethod according to claim 43, wherein said method further comprisescoupling said structure to a conductive member.
 48. A method fordetecting a pressure change in a volume, said method comprising:contacting a pressure sensor structure according to claim 1 with saidvolume; obtaining an output signal from said pressure sensor; and usingsaid output signal to detect a pressure change in said volume.
 49. Themethod according to claim 48, wherein said volume is present in asubject.
 50. The method according to claim 49, wherein said subject is ahuman.
 51. The method according to claim 50, wherein said methodcomprises implanting said sensor structure in said human.
 52. The methodaccording to claim 49, wherein said volume is a cardiovascular volume.53. The method according to claim 52, wherein said cardiovascular volumeis a heart chamber.
 54. The method according to claim 52, wherein saidcardiovascular volume is in an artery.
 55. The method according to claim49, wherein said method is a method of monitoring a condition in asubject.
 56. The method according to claim 55, wherein said methodcomprises monitoring said condition remotely.
 57. The method accordingto claim 55, wherein said condition is a cardiovascular condition. 58.The method according to claim 49, wherein said method is employed in amethod of one of: a) treating a subject for heart failure; b) performingcardiac resynchronization in a subject; c) managing arrhythmia in asubject; d) detecting ischemia in a subject; e) treating a subject forcoronary artery disease; f) monitoring heart valve function in asubject; and g) monitoring graft function in a subject.